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Biological Macromolecules: Bioactivity

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Kumar Nayak
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BIOLOGICAL MACROMOLECULES
BIOLOGICAL
MACROMOLECULES
BIOACTIVITY AND BIOMEDICAL
APPLICATIONS

Edited by

Amit Kumar Nayak


Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Jharpokharia, India

Amal Kumar Dhara


Department of Pharmacy, Contai Polytechnic, Contai, India

Dilipkumar Pal
Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya (A Central University),
Bilaspur, India
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Publisher: Andre G. Wolff


Acquisitions Editor: Michelle Fisher
Editorial Project Manager: Barbara Makinster
Production Project Manager: Swapna Srinivasan
Cover Designer: Matthew Limbert
Typeset by MPS Limited, Chennai, India
Contents

List of contributors xiii 2.2.2 Lysostaphin 28


2.2.3 Metallo-β-lactamase-like lactonase 32
Preface xix 2.3 Chitosan as a bioactive polysaccharide 36
2.3.1 Relationship of chitosan physicochemical
property and its bioactivity 37
I 2.3.2 Bioactivity of chitosan with modified
Background functional group 41
2.4 Conclusion 43
References 43
1. Biological macromolecules: sources,
properties, and functions 3. The importance of biological
AMAL KUMAR DHARA AND AMIT KUMAR NAYAK macromolecules in biomedicine
AHMED OLATUNDE, OMAR BAHATTAB, ABDUR RAUF,
1.1 Introduction 3 NAVEED MUHAMMAD, YAHYA S. AL-AWTHAN,
1.2 Carbohydrates 4 TABUSSAM TUFAIL, MUHAMMAD IMRAN AND
MOHAMMAD S. MUBARAK
1.2.1 Monosaccharides 5
1.2.2 Oligosaccharides 5
3.1 Introduction 53
1.2.3 Polysaccharides 5
3.2 Biological macromolecules in biomedicine and
1.3 Lipids 9
therapies 53
1.3.1 Simple lipids 10
3.3 Carbohydrates 54
1.3.2 Compound or conjugate lipids 10
3.3.1 Therapeutics based on carbohydrates 55
1.3.3 Derived lipids 10
3.4 Peptides 56
1.4 Proteins 11
3.4.1 Therapeutics based on peptides 57
1.4.1 Simple proteins 12
3.5 Proteins 58
1.4.2 Conjugated proteins 13
3.5.1 Therapeutics based on proteins (proteins
1.4.3 Derived proteins 13
and monoclonal antibodies) 58
1.5 Nucleic acids 14
3.6 Lipids 60
1.5.1 Nucleotides 15
3.6.1 Drug delivery-based on lipids 60
1.5.2 Nucleosides 15
3.7 Nucleic acids and oligonucleotides 61
1.5.3 DNA 15
3.7.1 Therapeutics based on oligonucleotides 61
1.5.4 RNA 16
3.8 Synthesis of macromolecules 63
1.6 Conclusion 18
3.9 Biomedicine 64
References 18
3.10 Conclusions 65
References 65
2. Structure activity relationship of
biological macromolecules
4. Modification techniques for
AURELIE SARAH MOK TSZE CHUNG, YONG KIAT TEO,
WAI TENG CHENG AND JOASH BAN LEE TAN carbohydrate macromolecules
AJAY VASUDEO RANE, DEEPTI YADAV
2.1 Introduction 23 AND KRISHNAN KANNY
2.2 Enzymes as bioactive proteins 24
2.2.1 L-amino acid oxidases 25 4.1 Introduction 69

v
vi Contents

4.2 Cellulose 69 5.8.1 Polyunsaturated fatty acids 120


4.3 Hemicelluloses 71 5.8.2 The role of Omega-3 PUFAs in some
4.4 Lignin 72 disorders 121
4.5 Chitin and chitosan 72 5.9 The potential use of bioactive lipids in cancer stem
4.6 Modification of carbohydrate biological cells and coronavirus disease (COVID-19) 123
macromolecules 73 5.9.1 Bioactive lipids in cancer 123
References 86 5.9.2 Bioactive lipids in COVID-19 123
5.10 Carbohydrates as nutraceuticals 124
5.10.1 Brief overview of carbohydrates 124
II 5.10.2 Role of polysaccharides in extracellular
membrane 124
Bioactivity 5.10.3 Immunostimmulatory effect of
carbohydrates 125
5. Biological macromolecules as 5.10.4 Carbohydrates from plants with
nutraceutical activity 125
nutraceuticals
5.10.5 Cellulose and hemicellulose 125
IRERI ALEJANDRA CARBAJAL-VALENZUELA, 5.10.6 Animal derived carbohydrates with
NUVIA MARINA APOLONIO HERNANDEZ,
DIANA VANESA GUTIERREZ-CHAVEZ,
nutraceutical activity 126
BEATRIZ GONZÁLEZ-ARIAS, 5.10.7 Heparin 126
ALEJANDRA JIMENEZ-HERNANDEZ, 5.10.8 Hyaluronic acid 127
IRINEO TORRES-PACHECO, ENRIQUE RICO-GARCÍA, 5.10.9 Chitosan and chitin 127
ANA ANGELICA FEREGRINO-PÉREZ
5.10.10 Carbohydrates with nutraceutical activity
AND RAMÓN GERARDO GUEVARA-GONZÁLEZ
from microorganisms 128
5.1 History of the applications of nutraceutical 5.10.11 Alginate 128
compounds in health care 97 5.10.12 Dextran 128
5.2 Alkaloids 99 5.10.13 Bacillus striatum polysaccharide 128
5.2.1 Caffeine 99 5.11 Credit 129
5.2.2 Capsaicin 101 References 129
5.2.3 Theobromine 101
5.3 Phenolic compounds 102 6. Biological macromolecules as
5.3.1 Curcumin 102 antioxidants
5.3.2 Resveratrol 103 T. MADHUJITH, N.E. WEDAMULLA AND D.A.S. GAMAGE
5.3.3 Quercetin 103
5.3.4 Anthocyanins 103 6.1 Introduction 139
5.3.5 Luteolin 104 6.2 Types and sources of biological
5.3.6 Naringenin 104 macromolecules 141
5.3.7 Catechins 104 6.2.1 Polysaccharides 141
5.4 Terpenes 105 6.2.2 Proteins 149
5.4.1 Lycopene 105 6.2.3 Other antioxidative macromolecules 152
5.4.2 β-Carotene 105 6.3 Macromolecules as antioxidants 152
5.4.3 Lutein 106 6.3.1 Polysaccharides as antioxidants 152
5.4.4 Zeaxanthin 107 6.3.2 Proteins as antioxidants 155
5.5 Future views 107 6.3.3 Nonextractable polyphenols as
5.6 Proteins and peptides with biological activity of antioxidants 156
medical interest 107 6.4 Applications 156
5.7 Nucleic acids and their nutraceutical properties 6.4.1 Food-based applications 156
used in biomedicine 112 6.4.2 Other applications 158
5.7.1 Nucleic acids overview 112 6.5 Limitations of biological macromolecules 158
5.7.2 Perspectives 119 6.6 Future trends 159
5.8 Introduction of lipids 119 References 159
Contents vii
7. Biological macromolecules as 8.2.1 Terpenoids 203
antimicrobial agents 8.2.2 Steroids 206
8.2.3 Phenolics 207
MD. SHAHRUZZAMAN, SHAFIUL HOSSAIN,
TANVIR AHMED, SUMAYA F. KABIR, 8.2.4 Alkaloids 208
MD. MINHAJUL ISLAM, ASHIQUR RAHMAN, 8.2.5 Polysaccharides 208
MD. SAZEDUL ISLAM, SABRINA SULTANA AND 8.2.6 Peptides 209
MOHAMMED MIZANUR RAHMAN 8.2.7 Polyketide 210
8.2.8 Polyunsaturated fatty acids 210
7.1 Introduction 165
8.3 Conclusion 213
7.2 Classification of biological macromolecule 167
References 213
7.2.1 Carbohydrate 167
7.2.2 Protein 169
7.2.3 Lipid 170 9. Biological macromolecules acting on
7.2.4 Nucleic acid 171
7.3 Antimicrobial activity of biological
central nervous system
macromolecules 172 DILIPKUMAR PAL AND KHUSHBOO RAJ

7.3.1 Polysaccharides 172


9.1 Introduction 219
7.3.2 Proteins 175
9.1.1 Proteins 219
7.3.3 Fatty acids 177
9.1.2 Cell cycle proteins 220
7.4 Antimicrobial activity of macromolecule
9.1.3 Homer/vesl proteins 220
composites 180
9.1.4 Central fatty hypothesis 222
7.4.1 Chitosan-alginate 180
9.1.5 Carbohydrates 222
7.4.2 Gelatin-chitosan 181
9.1.6 Role of carbohydrates on nervous
7.4.3 Keratin-chitosan 182
system 223
7.4.4 Collagen-alginate 183
9.1.7 In sensory organs 223
7.4.5 Chitosan-cellulose 184
9.1.8 Glycans 223
7.4.6 Lactoferrin-Oleic Acid 185
9.1.9 Role of glycan in neural development 224
7.5 Nanotechnology based antimicrobial
9.1.10 Lipids 224
macromolecule 185
9.1.11 Role of cPLA2 in cerebral ischemia 225
7.5.1 Chitosan based nanocomposite 185
9.1.12 In the case of neurodegenerative
7.5.2 Alginate-based nanocomposite 187
diseases 225
7.5.3 Cellulose based nanocomposite 187
9.1.13 Lipid peroxidation 225
7.5.4 Gelatin based nanocomposite 189
9.2 Conclusion 226
7.5.5 Collagen based nanocomposite 190
References 226
7.5.6 Keratin-based nanoparticle 190
7.5.7 Oleic acid based nanoparticle 190
7.6 Applications 190
7.6.1 Food packaging 190
10. Biological macromolecules as
7.6.2 Drug delivery 191 antidiabetic agents
7.6.3 Wound dressing 192 JAISON JEEVANANDAM, CALEB ACQUAH
7.7 Conclusion 193 AND MICHAEL K. DANQUAH

References 193
10.1 Introduction 229
8. Biological macromolecules from algae 10.2 Types of biological macromolecules 230
and their antimicrobial applications 10.3 Biological macromolecules 232
10.3.1 Carbohydrates 232
NATANAMURUGARAJ GOVINDAN,
GAANTY PRAGAS MANIAM, MOHD HASBI AB. RAHIM,
10.3.2 Lipids 233
AHMAD ZIAD SULAIMAN AND AZILAH AJIT 10.3.3 Proteins 235
10.3.4 Nucleic acids 237
8.1 Introduction 203 10.4 Advantages, limitations, and future
8.2 Bioactive macromolecules 203 perspectives 238
viii Contents

10.5 Conclusion 238 14. Synthetic macromolecules with


References 239 biological activity
STEFANIA RACOVITA, MARCEL POPA,
11. Biological macromolecules as LEONARD IONUT ATANASE AND SILVIA VASILIU
anticancer agents
HIMJA TIWARI, HARSHAL DESHMUKH,
14.1 Introduction 305
NILESH SHIRISH WAGH AND JAYA LAKKAKULA 14.2 Synthetic macromolecules with antimicrobial
activity 306
11.1 Introduction 243 14.2.1 History of antimicrobial agents and
11.2 Biological macromolecules for cancer therapy 244 antimicrobial polymers 307
11.2.1 Carbohydrates 244 14.2.2 Classification of antimicrobial
11.2.2 Proteins and nucleic acid 258 polymers 308
11.2.3 Lipids 262 14.2.3 Preparation routes for antimicrobial
11.3 Conclusion 269 polymers 309
References 269 14.2.4 Factors affecting the antimicrobial
activity 311
12. Biological macromolecules as 14.2.5 Synthetic macromolecules with
antibacterial activity 313
immunomodulators 14.2.6 Synthetic macromolecules with antiviral
EDUARDO COSTA, MANUELA MACHADO, activity 317
MANUELA PINTADO AND SARA SILVA
14.2.7 Synthetic macromolecules with antifungal
12.1 Introduction 273 activity 318
12.2 Immunomodulation 274 14.2.8 Synthetic macromolecules with
12.3 Immunomodulation, biomolecules, and antiparasitic activity 319
applications 274 14.3 Synthetic macromolecules with antioxidant
12.4 Polysaccharides 275 activity 320
12.4.1 Immunomodulatory polysaccharides 275 14.4 Polymer sequestrants 324
12.4.2 Gut microbiota modulation 277 14.5 Conclusions 328
12.5 Lipids 277 References 328
12.5.1 Immunomodulatory effect of lipids 278 Further reading 335
12.6 Proteins 280
12.6.1 Known immunomodulatory proteins 280 III
Acknowledgments 282
References 282 Functional applications
13. Biological macromolecules acting on 15. Biological macromolecules in drug
gastrointestinal systems delivery
DILIPKUMAR PAL AND SUPRIYO SAHA
AMIT KUMAR NAYAK, MD SAQUIB HASNAIN,
ANINDITA BEHERA, AMAL KUMAR DHARA AND
13.1 Introduction 289 DILIPKUMAR PAL
13.2 Role of carbohydrates in gastrointestinal
system 289 15.1 Introduction 339
13.3 Role of proteins in gastrointestinal system 295 15.2 Drug delivery using various biological
13.4 Role of fatty acids in gastrointestinal system 298 macromolecules 340
13.5 Role of nucleic acids in gastrointestinal 15.2.1 Drug delivery using carbohydrates 341
system 300 15.2.2 Drug delivery using proteins and
13.6 Conclusion 301 peptides 349
References 302 15.2.3 Drug delivery using nucleic acids 355
Contents ix
15.2.4 Drug delivery using lipids 359 18.4 Biological macromolecules for delivery systems of
15.3 Conclusion 367 growth factors 424
References 367 18.4.1 Protein-based materials for growth factor
delivery 425
16. Biological macromolecules in tissue 18.4.2 Polysaccharide-based materials for growth
engineering factor delivery 427
18.4.3 Polysaccharide combinations for growth
PANDURANG APPANA DALAVI,
SESHA SUBRAMANIAN MURUGAN, factor delivery 429
SUKUMARAN ANIL AND JAYACHANDRAN VENKATESAN 18.4.4 Composites materials for growth factor
delivery 430
16.1 Introduction 381 18.4.5 Protein-based composite for growth factor
16.2 Bone tissue engineering 381 delivery 430
16.3 Biological macromolecules in bone tissue 18.4.6 Protein-polysaccharide composites for
engineering 382 growth factor delivery 432
16.3.1 Alginate 382 18.4.7 Polysaccharide-polysaccharide composites
16.3.2 Chitosan 383 for growth factor delivery 433
16.3.3 Carrageenan 384 References 433
16.3.4 Fucoidan 385
16.3.5 Ulvan 385 19. Biological macromolecules for growth
16.3.6 Gelatin 386 factor delivery in bone regeneration
16.4 Conclusion 387
ARISTEIDIS PAPAGIANNOPOULOS AND ELENI VLASSI
Acknowledgment 387
References 387 19.1 Introduction 439
19.2 Bone regeneration 439
17. Biological macromolecules for drug 19.3 Growth factors in tissue and bone
delivery in tissue engineering regeneration 441
MARCEL POPA AND LEONARD IONUT ATANASE 19.4 Biomacromolecules as carriers of growth
factors 443
17.1 Introduction 393 19.5 Hydrogels and sponges 445
17.2 Drug-loaded electrospun fibers used in tissue 19.6 Scaffolds and fibers 446
engineering applications and drug delivery 394 19.7 Nanoparticles and nanoassemblies 448
17.2.1 Drug-loaded polysaccharides-based 19.8 Concluding remarks 449
electrospun fibers 395 References 449
17.2.2 Drug-loaded protein-based electrospun
fibers 401 20. Biological macromolecules for
17.3 Drug-loaded injectable hydrogels used in tissue nutrients delivery
engineering applications and drug delivery 403
LONG CHEN, ZHONGYU YANG, DAVID JULIAN
17.4 Conclusions 411 MCCLEMENTS, ZHENGYU JIN AND MING MIAO
References 411
20.1 Introduction 455
18. Biological macromolecules for growth 20.2 Nutrients 455
factor delivery 20.2.1 Water-soluble nutrients 456
M.D. FIGUEROA-PIZANO 20.2.2 Oil-soluble nutrients 458
20.3 Biological macromolecules used for nutrients
18.1 Introduction 419 delivery 458
18.2 Delivery systems for growth factors 421 20.3.1 Polysaccharides 459
18.3 Materials for delivery systems of growth 20.3.2 Proteins 461
factors 423 20.3.3 Glycoproteins and proteoglycans 461
x Contents

20.3.4 Others (lignin as example) 462 22.2.4 Collagen 500


20.4 Molecular interactions that maintain the stability 22.2.5 Gelatin 503
of biopolymer-based delivery systems 462 22.2.6 Fibrin 504
20.4.1 Electrostatic interactions 463 22.2.7 Glycosaminoglycans 505
20.4.2 Hydrogen bonding 463 22.2.8 Silk (fibroion and spidroin) 506
20.4.3 Hydrophobic interactions 463 22.2.9 Other natural polymers in TE 508
20.4.4 Covalent interactions 464 22.3 Advantages, drawbacks, applications, forms and
20.5 Retention and release mechanisms 464 manufacturing methods 511
20.6 Nutrient delivery systems based on biological 22.4 Conclusions 526
macromolecules 465 Acknowledgment 527
20.6.1 Composition and structure 465 References 527
20.6.2 Fabrication 466
20.6.3 Properties 469 23. Biological macromolecules for enzyme
20.6.4 Applications 469 immobilization
20.7 Future trends 471
HAMZA RAFEEQ, SARMAD AHMAD QAMAR,
20.7.1 Co-encapsulation of multiple HIRA MUNIR, MUHAMMAD BILAL AND HAFIZ M.N. IQBAL
nutrients 471
20.7.2 Targeted and controlled release of 23.1 Introduction 529
bioactive molecules 471 23.2 Biological macromolecules for enzyme
20.7.3 In vivo testing 472 immobilization 532
References 472 23.2.1 Chitin and chitosan 532
23.2.2 Agarose 533
21. Biological macromolecules for nucleic 23.2.3 Alginate 534
acid delivery 23.2.4 Cellulose and its derivatives 535
AHMED S. ABO DENA AND IBRAHIM M. EL-SHERBINY
23.2.5 Gelatin for enzyme immobilization 536
23.2.6 Dextran for enzyme immobilization 537
21.1 Introduction 479 23.2.7 Pectin for enzyme immobilization 539
21.2 Nucleic acids structure and functions 480 23.2.8 Xanthan for enzyme immobilization 540
21.3 Biological macromolecules for nucleic acid 23.3 Conclusions and future outlook 541
delivery 482 Acknowledgment 541
21.3.1 Lipid-based drug delivery systems 482 Conflicts of interest 541
21.3.2 Protein-based drug delivery systems 484 References 542
21.3.3 Carbohydrate-based drug delivery Further reading 546
systems 486
21.4 Conclusions 488 24. Carbohydrates mimetics: enzyme
References 489 inhibitors and target molecules in several
diseases
22. Biological macromolecules in cell VERÓNICA E. MANZANO, CUSTODIANA A.
encapsulation COLMENAREZ LOBO AND EVANGELINA REPETTO
MILAN MILIVOJEVIC, IVANA PAJIC-LIJAKOVIC AND
BRANKO BUGARSKI 24.1 Introduction 547
24.1.1 Biomass and biobased materials 547
22.1 Introduction 491 24.1.2 Carbohydrates 548
22.2 Biopolymers used for cell encapsulation in 24.1.3 Biological and medicinal interest of
TE 496 carbohydrates 550
22.2.1 Agarose 496 24.1.4 Glycosidases 551
22.2.2 Alginate 497 24.2 Glycomimetics 554
22.2.3 Chitin and chitosan 499 24.2.1 Iminosugars 554
Contents xi
24.2.2 Carbasugars 561 25.5.2 Gene delivery 592
24.2.3 Thiosugars 564 25.6 Macromolecules on tissue engineering 593
24.3 Hybrid carbohydrates 566 25.6.1 Wound management 597
24.4 Macromolecules 567 25.6.2 Development of skin substitutes 597
24.4.1 Multivalents 567 25.7 Conclusion 600
24.4.2 Polysaccharides 569 References 600
24.5 Conclusions 570
References 570 26. Future perspectives of biological
macromolecules in biomedicine
IV ANA R. NEVES, RÚBEN FARIA, TÂNIA ALBUQUERQUE,
TELMA QUINTELA, ÂNGELA SOUSA AND DIANA COSTA

Others 26.1 Bio-nanotechnology 607


26.1.1 Delivery systems 608
25. Current challenging issues of 26.2 Mitochondrial gene therapy 610
biological macromolecules in biomedicine 26.2.1 Mitochondrion 611
26.2.2 Mitochondrial mutations 611
Y. DE ANDA-FLORES, E. CARVAJAL-MILLAN,
A.C. CAMPA-MADA, K.G. MARTÍNEZ-ROBINSON,
26.2.3 Targeting Mitochondria 612
J. LIZARDI-MENDOZA, A. RASCÓN-CHU, 26.3 Crosstalk between chronobiology and cancer 616
A.L. MARTÍNEZ-LÓPEZ AND J. TANORI-CORDOVA 26.3.1 Circadian clock and cancer
development 617
25.1 Introduction 581 26.3.2 Chronobiology and cancer treatment 619
25.2 Biological macromolecules 582 26.4 Concluding remarks 624
25.3 Macromolecules in biomedical applications 583 References 625
25.4 Macromolecules in targeted drug delivery 584
25.5 Biomaterials as targeted drug delivery 585 Index 633
25.5.1 Hydrogels for drug delivery 585
List of contributors

Ahmed S. Abo Dena Nanomedicine Laboratory, Anindita Behera School of Pharmaceutical


Center for Materials Science, Zewail City of Sciences, Siksha “O” Anusandhan, Deemed to be
Science and Technology, Giza, Egypt; University, Bhubaneswar, India
Department of Pharmaceutical Chemistry, Muhammad Bilal School of Life Science and Food
National Organization for Drug Control and Engineering, Huaiyin Institute of Technology,
Research (NODCAR), Giza, Egypt Huai’an, China
Caleb Acquah School of Nutrition Sciences, Branko Bugarski Department of Chemical
Faculty of Health Sciences, University of Ottawa, Engineering, Faculty of Technology and Metallurgy,
Ottawa, ON, Canada University of Belgrade, Belgrade, Serbia
Tanvir Ahmed Department of Applied Chemistry A.C. Campa-Mada Biopolymers-CTAOA,
and Chemical Engineering, Faculty of Research Center for Food and Development
Engineering and Technology, University of (CIAD, A.C.), Hermosillo, Mexico
Dhaka, Dhaka, Bangladesh
Ireri Alejandra Carbajal-Valenzuela Biosystems
Azilah Ajit Faculty of Chemical & Natural Engineering Group, School of Engineering-
Resources Engineering, Universiti Malaysia Campus Amazcala, Autonomous University of
Pahang, Kuantan, Malaysia Querétaro (México), Querétaro, México
Yahya S. Al-Awthan Department of Biology, E. Carvajal-Millan Biopolymers-CTAOA, Research
Faculty of Science, University of Tabuk, Tabuk, Center for Food and Development (CIAD, A.C.),
Saudia Arabia; Department of Biology, Faculty of Hermosillo, Mexico
Science, Ibb University, Ibb, Yemen
Long Chen School of Food Science and
Tânia Albuquerque CICS-UBI—Health Sciences Technology, Jiangnan University, Wuxi, P.R.
Research Centre, University of Beira Interior, China; State Key Laboratory of Food Science and
Covilhã, Portugal Technology, Jiangnan University, Wuxi, P.R. China
Sukumaran Anil Department of Dentistry, Oral Wai Teng Cheng School of Science, Monash
Health Institute, Hamad Medical Corporation, University Malaysia, Bandar Sunway, Malaysia
College of Dental Medicine, Qatar University,
Custodiana A. Colmenarez Lobo Research Center
Doha, Qatar
in Carbohydrate Chemistry (CIHIDECAR),
Nuvia Marina Apolonio–Hernandez Biosystems National Scientific and Technical Research
Engineering Group, School of Engineering- Council (CONICET)-UBA, Buenos Aires,
Campus Amazcala, Autonomous University of Argentina
Querétaro (México), Querétaro, México
Diana Costa CICS-UBI—Health Sciences Research
Leonard Ionut Atanase Academy of Romanian Centre, University of Beira Interior, Covilhã,
Scientists, Bucuresti, Romania; Faculty of Dental Portugal
Medicine, “Apollonia” University of Iasi, Iasi, Eduardo Costa Universidade Católica Portuguesa,
Romania CBQF—Centro de Biotecnologia e Quı́mica Fina
Omar Bahattab Department of Biology, Faculty of —Laboratório Associado, Escola Superior de
Science, University of Tabuk, Tabuk, Saudia Arabia Biotecnologia, Porto, Portugal

xiii
xiv List of contributors

Pandurang Appana Dalavi Biomaterials Research Diana Vanesa Gutierrez-Chavez Biosystems


Laboratory, Yenepoya Research Centre, Engineering Group, School of Engineering-
Yenepoya (Deemed to be University), Campus Amazcala, Autonomous University of
Deralakatte, Mangalore, India Querétaro (México), Querétaro, México
Michael K. Danquah Chemical Engineering Md Saquib Hasnain Department of Pharmacy,
Department, University of Tennessee, Palamau Institute of Pharmacy, Daltonganj, India
Chattanooga, TN, United States Shafiul Hossain Department of Applied
Y. De Anda-Flores Biopolymers-CTAOA, Research Chemistry and Chemical Engineering, Faculty of
Center for Food and Development (CIAD, A.C.), Engineering and Technology, University of
Hermosillo, Mexico Dhaka, Dhaka, Bangladesh; Department of
Chemical Engineering and Polymer Science,
Harshal Deshmukh Amity Institute of
Shahjalal University of Science and Technology,
Biotechnology, Amity University Maharashtra,
Sylhet, Bangladesh
Mumbai, —Pune Expressway, Bhatan Post—
Somathne, Panvel, Mumbai, India Muhammad Imran University Institute of Diet &
Nutritional Sciences, Faculty of Allied Health
Amal Kumar Dhara Department of Pharmacy, Sciences, The University of Lahore, Lahore,
Contai Polytechnic, Contai, India Pakistan
Ibrahim M. El-Sherbiny Nanomedicine Hafiz M.N. Iqbal Tecnologico de Monterrey,
Laboratory, Center for Materials Science, Zewail School of Engineering and Sciences, Monterrey,
City of Science and Technology, Giza, Egypt Mexico
Rúben Faria CICS-UBI—Health Sciences Research Jaison Jeevanandam CQM—Centro de Quı́mica
Centre, University of Beira Interior, Covilhã, da Madeira (Madeira Chemistry Center), MMRG,
Portugal Universidade da Madeira (University of
Ana Angelica Feregrino-Pérez Biosystems Madeira), Campus da Penteada (Penteada cam-
Engineering Group, School of Engineering- pus), Funchal, Portugal
Campus Amazcala, Autonomous University of Alejandra Jimenez-Hernandez Biosystems
Querétaro (México), Querétaro, México Engineering Group, School of Engineering-
M.D. Figueroa-Pizano Biopolymers-CTAOA, Campus Amazcala, Autonomous University of
Research Center for Food and Development Querétaro (México), Querétaro, México
(CIAD), Hermosillo, Sonora, Mexico Zhengyu Jin School of Food Science and
D.A.S. Gamage Department of Chemical and Technology, Jiangnan University, Wuxi, P.R.
Process Engineering, Faculty of Engineering, China; State Key Laboratory of Food Science and
University of Peradeniya, Peradeniya, Sri Technology, Jiangnan University, Wuxi, P.R.
Lanka China
Beatriz González-Arias Biosystems Engineering Sumaya F. Kabir Department of Applied
Group, School of Engineering-Campus Amazcala, Chemistry and Chemical Engineering, Faculty of
Autonomous University of Querétaro (México), Engineering and Technology, University of
Querétaro, México Dhaka, Dhaka, Bangladesh
Natanamurugaraj Govindan Algae Culture Krishnan Kanny Composite Research Group,
Collection Center & Laboratory, Faculty of Department of Mechanical Engineering, Durban
Industrial Sciences and Technology, Universiti University of Technology, Durban, South Africa
Malaysia Pahang, Kuantan, Malaysia; Centre for Jaya Lakkakula Amity Institute of Biotechnology,
Research in Advanced Tropical Bioscience, Amity University Maharashtra, Mumbai, —Pune
Universiti Malaysia Pahang, Kuantan, Malaysia Expressway, Bhatan Post—Somathne, Panvel,
Ramón Gerardo Guevara-González Biosystems Mumbai, India
Engineering Group, School of Engineering- J. Lizardi-Mendoza Biopolymers-CTAOA,
Campus Amazcala, Autonomous University of Research Center for Food and Development
Querétaro (México), Querétaro, México (CIAD, A.C.), Hermosillo, Mexico
List of contributors xv
Manuela Machado Universidade Católica Mohammad S. Mubarak Department of
Portuguesa, CBQF—Centro de Biotecnologia e Chemistry, The University of Jordan, Amman,
Quı́mica Fina—Laboratório Associado, Escola Jordan
Superior de Biotecnologia, Porto, Portugal Naveed Muhammad Department of Pharmacy,
T. Madhujith Department of Food Science and Abdul Wali Khan University, Khyber
Technology, Faculty of Agriculture, University of Pakhtunkhwa, Pakistan
Peradeniya, Peradeniya, Sri Lanka Hira Munir Department of Biochemistry and
Gaanty Pragas Maniam Algae Culture Collection Biotechnology, University of Gujrat, Gujrat,
Center & Laboratory, Faculty of Industrial Pakistan
Sciences and Technology, Universiti Malaysia Sesha Subramanian Murugan Biomaterials
Pahang, Kuantan, Malaysia; Centre for Research Research Laboratory, Yenepoya Research Centre,
in Advanced Tropical Bioscience, Universiti Yenepoya (Deemed to be University),
Malaysia Pahang, Kuantan, Malaysia Deralakatte, Mangalore, India
Verónica E. Manzano Faculty of Exact and Amit Kumar Nayak Department of
Natural Sciences, Department of Organic Pharmaceutics, Seemanta Institute of
Chemistry, University of Buenos Aires, Buenos Pharmaceutical Sciences, Jharpokharia, India
Aires, Argentina; Research Center in
Carbohydrate Chemistry (CIHIDECAR), National Ana R. Neves CICS-UBI—Health Sciences
Scientific and Technical Research Council Research Centre, University of Beira Interior,
(CONICET)-UBA, Buenos Aires, Argentina Covilhã, Portugal
Ahmed Olatunde Department of Biochemistry,
A.L. Martı́nez-López NANO-VAC Research
Abubakar Tafawa Balewa University, Bauchi,
Group, Department of Chemistry and
Nigeria
Pharmaceutical Technology, University of
Navarra, Pamplona, Spain Ivana Pajic-Lijakovic Department of Chemical
Engineering, Faculty of Technology and
K.G. Martı́nez-Robinson Biopolymers-CTAOA,
Metallurgy, University of Belgrade, Belgrade,
Research Center for Food and Development
Serbia
(CIAD, A.C.), Hermosillo, Mexico
Dilipkumar Pal Department of Pharmaceutical
David Julian McClements Department of Food Sciences, Guru Ghasidas Vishwavidyalaya (A
Science, University of Massachusetts, Amherst, Central University), Bilaspur, India
MA, United States
Aristeidis Papagiannopoulos Theoretical and
Ming Miao School of Food Science and Physical Chemistry Institute, National Hellenic
Technology, Jiangnan University, Wuxi, P.R. Research Foundation, Athens, Greece
China; State Key Laboratory of Food Science and
Manuela Pintado Universidade Católica
Technology, Jiangnan University, Wuxi, P.R.
Portuguesa, CBQF—Centro de Biotecnologia e
China
Quı́mica Fina—Laboratório Associado, Escola
Milan Milivojevic Department of Chemical Superior de Biotecnologia, Porto, Portugal
Engineering, Faculty of Technology and
Marcel Popa “Apollonia” University of Iasi,
Metallurgy, University of Belgrade, Belgrade,
Faculty of Dental Medicine, Iasi, Romania;
Serbia
Academy of Romanian Scientists, Bucuresti,
Md. Minhajul Islam Department of Applied Romania; Faculty of Chemical Engineering and
Chemistry and Chemical Engineering, Faculty of Environmental Protection, Department of Natural
Engineering and Technology, University of and Synthetic Polymers, “Gheorghe Asachi”
Dhaka, Dhaka, Bangladesh Technical University of Iasi, Iasi, Romania
Aurelie Sarah Mok Tsze Chung School of Science, Sarmad Ahmad Qamar Department of
Monash University Malaysia, Bandar Sunway, Biochemistry, University of Agriculture,
Malaysia Faisalabad, Pakistan
xvi List of contributors

Telma Quintela CICS-UBI—Health Sciences Supriyo Saha School of Pharmaceutical Sciences


Research Centre, University of Beira Interior, and Technology, Sardar Bhagwan Singh
Covilhã, Portugal University, Dehradun, India
Stefania Racovita “Petru Poni” Institute of Md. Sazedul Islam Department of Applied
Macromolecular Chemistry, Iasi, Romania Chemistry and Chemical Engineering, Faculty of
Engineering and Technology, University of
Hamza Rafeeq Department of Biochemistry, Dhaka, Dhaka, Bangladesh
University of Agriculture, Faisalabad, Pakistan
Md. Shahruzzaman Department of Applied
Mohd Hasbi Ab. Rahim Algae Culture Collection Chemistry and Chemical Engineering, Faculty of
Center & Laboratory, Faculty of Industrial Engineering and Technology, University of
Sciences and Technology, Universiti Malaysia Dhaka, Dhaka, Bangladesh
Pahang, Kuantan, Malaysia; Centre for Research
Sara Silva Universidade Católica Portuguesa,
in Advanced Tropical Bioscience, Universiti
CBQF—Centro de Biotecnologia e Quı́mica Fina
Malaysia Pahang, Kuantan, Malaysia
—Laboratório Associado, Escola Superior de
Ashiqur Rahman Department of Applied Biotecnologia, Porto, Portugal
Chemistry and Chemical Engineering, Faculty of Ângela Sousa CICS-UBI—Health Sciences
Engineering and Technology, University of Research Centre, University of Beira Interior,
Dhaka, Dhaka, Bangladesh; National Institute of Covilhã, Portugal
Textile Engineering and Research (NITER),
Ahmad Ziad Sulaiman Faculty of Bio-Engineering
Dhaka, Bangladesh
& Technology, University Malaysia Kelantan
Mohammed Mizanur Rahman Department of Kampus Jeli, Kelantan, Malaysia
Applied Chemistry and Chemical Engineering, Sabrina Sultana Department of Applied
Faculty of Engineering and Technology, Chemistry and Chemical Engineering, Faculty of
University of Dhaka, Dhaka, Bangladesh Engineering and Technology, University of
Khushboo Raj School of Pharmacy, Arka Jain uni- Dhaka, Dhaka, Bangladesh; Department of Arts
versity, Tata, Jamshedpur, India and Sciences, Ahsanullah University of Science
and Technology, Dhaka, Bangladesh
Ajay Vasudeo Rane Composite Research Group,
Department of Mechanical Engineering, Durban Joash Ban Lee Tan School of Science, Monash
University of Technology, Durban, South Africa University Malaysia, Bandar Sunway, Malaysia
A. Rascón-Chu Biotechnology-CTAOV, Research J. Tanori-Cordova Department of Polymers and
Center for Food and Development (CIAD, A.C.), Materials Research, University of Sonora,
Hermosillo, Mexico Hermosillo, Mexico
Yong Kiat Teo School of Science, Monash
Abdur Rauf Department of Chemistry, University
University Malaysia, Bandar Sunway, Malaysia
of Swabi Anbar, Khyber Pakhtunkhwa, Pakistan
Himja Tiwari Amity Institute of Biotechnology,
Evangelina Repetto Faculty of Exact and Natural Amity University Maharashtra, Mumbai, —Pune
Sciences, Department of Organic Chemistry, Expressway, Bhatan Post—Somathne, Panvel,
University of Buenos Aires, Buenos Aires, Mumbai, India
Argentina; Research Center in Carbohydrate
Irineo torres-Pacheco Biosystems Engineering
Chemistry (CIHIDECAR), National Scientific and
Group, School of Engineering-Campus Amazcala,
Technical Research Council (CONICET)-UBA,
Autonomous University of Querétaro (México),
Buenos Aires, Argentina
Querétaro, México
Enrique Rico-Garcı́a Biosystems Engineering Tabussam Tufail University Institute of Diet &
Group, School of Engineering-Campus Amazcala, Nutritional Sciences, Faculty of Allied Health
Autonomous University of Querétaro (México), Sciences, The University of Lahore, Lahore,
Querétaro, México Pakistan
List of contributors xvii
Silvia Vasiliu “Petru Poni” Institute of N.E. Wedamulla Department of Export
Macromolecular Chemistry, Iasi, Romania Agriculture, Faculty of Animal Science and
Jayachandran Venkatesan Biomaterials Research Export Agriculture, Uva Wellassa University,
Laboratory, Yenepoya Research Centre, Badulla, Sri Lanka
Yenepoya (Deemed to be University), Deepti Yadav Department of Biotechnology and
Deralakatte, Mangalore, India Food Science, Durban University of Technology,
Eleni Vlassi Theoretical and Physical Chemistry Durban, South Africa
Institute, National Hellenic Research Foundation, Zhongyu Yang School of Food Science and
Athens, Greece Technology, Jiangnan University, Wuxi, P.R.
Nilesh Shirish Wagh Amity Institute of China
Biotechnology, Amity University Maharashtra,
Mumbai, —Pune Expressway, Bhatan Post—
Somathne, Panvel, Mumbai, India
Preface

The scope of this book, entitled Biological This book, containing 4 sections and 26
Macromolecules: Bioactivity and Biomedical chapters, provides a systematic insight into the
Applications, is the coverage and review of inclusive discussions on bioactivity and bio-
recent trends and applications of biological medical applications of different biological
macromolecules, such as carbohydrates, lipids, macromolecules. We are glad to see that many
proteins, peptides, and nucleic acids in biome- authors across the globe accepted our invita-
dicines, drug delivery, growth factors delivery, tion and contributed valued chapters for this
nutrients and nucleic acids delivery, cell encap- book, covering a wide spectrum of fields. A
sulation, enzyme mobilization, and tissue concise account of the contents of each chapter
engineering. has been described to provide a glimpse of the
The mysteries of life lie in biological macro- book to the potential readers of various fields.
molecules. A large volume of biological macro- The topics in the book (in order of prefer-
molecules is obtained from different biological ence) include the following: Biological
origins such as plants, algae, fungi, animals, Macromolecules: Sources, Properties, and functions
and microbial sources. Biological macromole- (Chapter 1)—this chapter describes sources
cules exhibit some significant and favorable physicochemical properties, bioactivity and
advantages over synthetic macromolecules, biomedical applications of different biological
such as sustainable and economic production, macromolecules concisely; Structure Activity
biocompatibility, biodegradability, and Relationship of Biological Macromolecules
improved bioavailability. In recent years, a (Chapter 2)—this chapter aims to provide an
plethora of biological macromolecules (carbo- overview of the structural features influencing
hydrates, lipids, proteins, peptides, and nucleic the bioactivities of biological macromolecules,
acids) has been used in the biomedical and namely L-amino acid oxidases, lysostaphin,
healthcare fields. They showed varieties of and metallo-β-lactamase-such as lactonase and
bioactivities such as antioxidant, anticancer, chitosan; The Importance of Biological
antidiabetic, antimicrobial, immunomodula- Macromolecules in Biomedicine (Chapter 3)—this
tory activities on the central nervous system, chapter highlights the therapeutic aspects of
and gastrointestinal activity. The other biomed- macromolecules and the medicinal use of bio-
ical applications include drug delivery, growth logical macromolecules against various dis-
factors delivery, nutrients and nucleic acids eases and ailments; Modification Techniques for
delivery, cell encapsulation, enzyme mobiliza- Carbohydrate Macromolecules (Chapter 4)—this
tion, and tissue engineering. The structure- chapter characteristically abridges the signifi-
property relationship is also an important cant developments of the last five to ten years
aspect for a thorough understanding of the bio- and discusses critically in the area of modifica-
activity of biological macromolecules. tion of carbohydrates macromolecules;

xix
xx Preface

Biological Macromolecules as Nutraceuticals discussed briefly along with several assays


(Chapter 5)—this chapter aims to demonstrate done to evaluate cytotoxicity of the macromole-
some recent knowledge regarding the nutra- cules against various cancers such as lung can-
ceutical and biological activities of the macro- cer, breast cancer, cervical cancer, and colon
molecules of biological origin, as well as some cancer. Biological Macromolecules as
frontier applications of these in healthcare; Immunomodulators (Chapter 12)—this topic
Biological Macromolecules as Antioxidants focuses on the potential modulations of
(Chapter 6)—this chapter highlights the poten- immune response of biomacromolecules (three
tial applications of biological macromolecules major classes of compounds: lipids, proteins
as antioxidants to scavenge reactive oxygen and polysaccharides); Biological Macromolecules
species and control oxidative stress, which Acting on Gastrointestinal Systems
leads to various pathogenesis; Biological (Chapter 13)—this chapter describes the role of
Macromolecules as Antimicrobial Agents biological macromolecules for the management
(Chapter 7)—the chapter describes the antimi- of gastrointestinal system and related disor-
crobial activity of biological macromolecules ders; Synthetic Macromolecules With Biological
(chitosan, cellulose, alginate, gelatin, collagen, Activity (Chapter 14)—this chapter describes
and keratin) and also, comprehensively eluci- some classes of synthetic macromolecules with
dates their applications in addressing chal- biological activity that have a great importance
lenges associated with drug delivery, wound on the human comfort and health, including
dressing, food packaging, and so on Biological antimicrobial polymers, antioxidant polymers,
Macromolecules From Algae and Their and polymeric sequestrants; Biological
Antimicrobial Applications (Chapter 8) this Macromolecules in Drug Delivery (Chapter 15)—
chapter provides an overview of bioactive this chapter focuses on the advancements in
macromolecules and their antimicrobial activi- the uses of various biological macromolecules
ties with particular reference to algal sources; in drug delivery applications; Biological macro-
Biological Macromolecules Acting on Central molecules in tissue engineering (Chapter 16)—this
Nervous System (Chapter 9)—in this chapter, chapter provides an overview on the important
the role of biological macromolecules on cen- role of natural-derived biomaterials (alginate,
tral nervous system and their critical role in chitosan, carrageenan, fucoidan, ulvan, colla-
downregulation after the various neurological gen, and gelatin) combining with ceramic bio-
disorders have been discussed; Biological materials for bone tissue construction;
Macromolecules as Antidiabetic Agents Biological Macromolecules for Drug Delivery in
(Chapter 10)—this chapter is an overview of Tissue Engineering (Chapter 17)—This chapter
different types of biological macromolecules is focused on the preparation and physico-
and their applications as potential antidiabetic chemical characterization of engineered bioma-
agents and also, highlights the advantages, lim- terials, based on biological macromolecules
itations and future perspectives of biological (polysaccharides and proteins), as scaffolds
macromolecules as antidiabetic agents; which are capable of supporting physiological
Biological Macromolecules as Anticancer Agents activities of cells, but also can act as drug deliv-
(Chapter 11)—this chapter presents the extrac- ery systems for tissue engineering and wound
tion of macromolecules such as carbohydrate, healing; Biological Macromolecules for Growth
proteins, lipids, and nucleic acid (miRNAs) Factor Delivery (Chapter 18)—this chapter dis-
from different biological sources, such as cusses the fabrication of synthetic and natural
plants, animal, algae and fungi. The various macromolecules, sometimes combined with
mechanisms by which the macromolecules other mineral or metallic compounds for
exhibit their anticancer activity have been growth factor delivery; Biological
Preface xxi
Macromolecules for Growth Factor Delivery in inhibition of these enzymes constitutes an
Bone Regeneration (Chapter 19)—this chapter interesting and novel strategy to approach new
describes the process of bone tissue regenera- therapies against numerous diseases; Current
tion in healing injuries and arthritic conditions, Challenging Issues of Biological Macromolecules in
introduces the main ideas through the scope of Biomedicine (Chapter 25)—this chapter provides
allogenous and autogenous transplantation information on recent innovations in various
and demonstrates the role of growth factors in biomaterials, engineered from macromolecules
these processes; Biological Macromolecules for ranging from drug delivery, cancer therapies,
Nutrients Delivery (Chapter 20)—This chapter tissue engineering, bioprinting and wound
focuses on the types of nutrients that need to healing; Future Perspectives of Biological
be delivered, the biological macromolecules Macromolecules in Biomedicine (Chapter 26)—
that can be used to construct edible delivery this chapter discusses the impact of the combi-
systems, the most common delivery systems nation of nanotechnology and chronobiology
currently used for this purpose, and some of in personalized cancer treatment.
the major challenges that must be addressed in We sincerely acknowledge the valuable con-
the future; Biological Macromolecules for Nucleic tribution of the distinguished authors and con-
Acid Delivery (Chapter 21)—this chapter vey our sincere thanks. This book could not
describes the nonviral nucleic acid delivery have been published without the cooperation
systems made up of biological macromole- of Barbara Makinster, Editorial Project
cules, such as peptides, lipids, and carbohy- Manager. We wish to express our cordial grati-
drates and also gives an introduction on the tude to Elsevier Inc., Michelle Fisher
history and structure of nucleic acids; Biological (Acquisition Editor), and other editorial staff
Macromolecules in Cell Encapsulation for their invaluable supports in organizing the
(Chapter 22)—this chapter aims to review the intelligent editing of the book. We also grate-
most examined, most promising and recently fully acknowledge all the permissions we
proposed biopolymers that are used in tissue received for reproducing the copyright materi-
engineering scaffolds, and to highlight their als from different sources. Finally, we cannot
main properties, drawbacks, fields of applica- overlook the sacrifices and supports from our
tions and fabrication technologies in order to family members during the preparation of the
provide readers with important guidelines for current book. All our friends, colleagues, and
selecting appropriate scaffold biomaterials; students who have helped in the process of
Biological Macromolecules for Enzyme editing this book deserve our great apprecia-
Immobilization (Chapter 23)—this chapter pro- tion. Contributing authors, the publishers, and
vides a broad overview of properties and the we, the editors, will be extremely happy if our
applications of various naturally occurring bio- endeavor fulfills the needs of the academicians,
polymers, that is, chitosan, chitin, agarose, algi- researchers, students, pharmaceutical experts,
nates, cellulose, gelatin, dextran, carrageenan, biomedicine experts, and formulators.
pectin and xanthan gum for their applications Amit Kumar Nayak1, Amal Kumar Dhara2
in enzyme immobilization with recent litera- and Dilipkumar Pal3
ture studies indicating biopolymer-based sup- 1
Department of Pharmaceutics, Seemanta Institute
port material development and their utilization of Pharmaceutical Sciences, Jharpokharia, India
to make biocatalysts with desired stability and 2
Department of Pharmacy, Contai Polytechnic,
catalytic functionalities; Carbohydrates for Govt. of West Bengal, Contai, India 3Department of
Enzyme Inhibition and Their Use as Target Pharmaceutical Sciences, Guru Ghasidas
Molecules for the Interference of Diseases Vishwavidyalaya (A Central University), Bilaspur,
(Chapter 24)—this chapter describes the study India
of a widespread group of enzymes and the
C H A P T E R

1
Biological macromolecules: sources,
properties, and functions
Amal Kumar Dhara1 and Amit Kumar Nayak2
1
Department of Pharmacy, Contai Polytechnic, Contai, India 2Department of Pharmaceutics, Seemanta
Institute of Pharmaceutical Sciences, Jharpokharia, India

1.1 Introduction (RNA) are responsible for carrying genetic


blueprint and information for protein synthesis
The mystery of life is in biological macromo- (Minchin & Lodge, 2019; Schwartz, Schwartz,
lecules. There are four important classes of bio- Mieszerski, McNally, & Kobilinsky, 1991).
logical macromolecules, viz., carbohydrates, Biological macromolecules are abundantly
lipids, proteins, and nucleic acids (Luo, Zhang, available in nature and also possess properties
Wu, Liang, & Li, 2020; Zhang, Sun, & Jiang, like biocompatibility, environmental friendly,
2018). Carbohydrates, proteins, and nucleic biodegradability, etc., because of their natural
acids naturally exist as long chain polymers, sources (Chandika et al., 2020; Teramoto, 2020).
while lipids are smaller and in true sense, these Various species of algae have been mentioned
are all considered as biopolymers (Albertsson, to be used as bioactive compounds and are
2019; Teramoto, 2020; Zhang et al., 2018). also employed as antibacterial agents (Shannon
Carbohydrates are the storage form of energy & Abu-Ghannam, 2016). Various disorders
and meet the demand as and when required related to central nervous system, such as
(Slavin & Carlson, 2014). Lipids are also stor- Alzheimer’s disease, Parkinson’s disease, con-
age form of energy and are the important vulsive disorders, etc., are being treated with
structural components of the cell membrane the biological macromolecules (Acosta &
(van Meer, Voelker, & Feigenson, 2008; Zheng, Cramer, 2020; Soderquist & Mahoney, 2010;
Fleith, Giuffrida, O’Neill, & Schneider, 2019). Zhang et al., 2018). All the biological macromo-
Proteins serve several functions including lecules, viz., carbohydrates, lipids, proteins
structural support, catalyzing important meta- and nucleic acids, have shown their significant
bolic reactions, signals receiving and transmis- role in the management of cancer therapy and
sion, etc. (Watford & Wu, 2018; Zaretsky & have been advocated to be used against vari-
Wreschner, 2008). Nucleic acids, that is, deox- ous cancers like lung cancer, colon cancer,
yribonucleic acid (DNA) and ribonucleic acid breast cancer, cervical cancer, etc.

Biological Macromolecules
DOI: https://doi.org/10.1016/B978-0-323-85759-8.00005-1 3 © 2022 Elsevier Inc. All rights reserved.
4 1. Biological macromolecules: sources, properties, and functions

(Corn, Windham, & Rafat, 2020; Oana, (Hasnain et al., 2020; Kandar, Hasnain, &
Adriana, Mircea, Dragos, & Monica, 2018; Nayak, 2021; Maity et al., 2021; Nayak &
Rodrigues Mantuano, Natoli, Zippelius, & Hasnain, 2019a, 2019b; Nayak, Hasnain, Dhara,
Läubli, 2020; Sun, Jing, Ma, Feng, & Hu, 2020). & Pal, 2021; Pal, Saha, Nayak et al., 2019).
Another important area of research is immuno- Polysaccharide and proteins are used exten-
modulators with respect to present SARS-CoV-2 sively for the preparation of hydrogels for
perspective, where the biological macromole- drug delivery, tissue regeneration, wound
cules, mainly proteins, play significant role (Ji dressings, etc. (Del Valle, Dı́az, & Puiggalı́,
et al., 2020). Proteins are associated with the 2017; Nayak & Pal, 2016b; Nayak, Hasnain,
development process of immune system (Daly, Pal, Banerjee, & Pal, 2020; Pal, Nayak, & Saha,
Reynolds, Sigal, Shou, & Liberman, 1990). 2019a, 2019b; Ray et al., 2020). Beside drug
Lipids are also responsible to play key role as delivery, the biological macromolecules have
adjuvants for the development of vaccines continuously been used to formulate delivery
(Martinez-Gil, Goff, & Tan, 2018; Schwendener, carrier-systems for growth factors (Rao, Rekha,
2014). Day by day, the incidence of lifestyle Anil, Lowe, & Venkatesan, 2019; Shariatinia,
diseases more specifically diabetes, hyperten- 2019). Polysaccharides are also employed for
sion, etc., are increasing vertically, where the the encapsulation of various bioactive sub-
roles of biological macromolecules have been stances like vitamins and nutraceuticals (Bala,
studied and were found to be utilized widely Singha, & Patra, 2019; Lauro, Amato, Sansone,
as antidiabetic agents (Alam, Shafique, Amjad, Carbone, & Puglisi, 2019). The current chapter
& Bin Asad, 2019; Hu, Nie, & Xie, 2018; Rı́os, deals with a brief discussion about the sources,
Francini, & Schinella, 2015; Yu, Shen, Song, & properties, and valuable applications of vari-
Xie, 2018). They cause increase in insulin secre- ous biological macromolecules like carbohy-
tion and thus, reduce the blood glucose level drates, lipids, proteins and nucleic acids.
(Rı́os et al., 2015). Chitosan is a well-known
polysaccharide, which is reported to exhibit
antimicrobial and antidiabetic activities
(Hasnain & Nayak, 2018; Karadeniz & Kim, 1.2 Carbohydrates
2014; Rabea, Badawy, Stevens, Smagghe, &
Steurbaut, 2003). Extensive research is going The most widely found organic compounds
on in the area of tissue engineering for the in nature are carbohydrates. These are well-
development of artificial tissue to repair and known as very essential source of life or sus-
replace defective or diseased tissue or organs taining life itself (Slavin & Carlson, 2014).
(Hasnain, Ahmad, Chaudhary, Hoda, & Carbohydrates are commonly found in plants,
Nayak, 2019; Nayak, Ahmed, Tabish, & microorganisms and animal tissues (Werz &
Hasnain, 2019; Pal, Saha, Nayak, & Hasnain, Seeberger, 2005). These are also present in
2019). Naturally derived biological macromole- blood, tissue fluids, etc. (Kilcoyne & Joshi,
cules like chitosan, alginate, carrageenan, 2007). Carbon, hydrogen and oxygen are the
ulvan, gelatin, etc., have been used for three primary elements of molecular structure
bone tissue regeneration (Hasnain, Nayak, of carbohydrates (Luo et al., 2020; Werz &
Singh, & Ahmad, 2010; Maity, Hasnain, Nayak, Seeberger, 2005). These are optically active
& Aminabavi, 2021; Nayak, Ahmed, Tabish, & polyhydroxy aldehydes or ketones. There are
Hasnain, 2019). Numbers of polysaccharide three major classes of carbohydrates, broadly,
have long been used in different types of drug monosaccharides, oligosaccharides and poly-
delivery systems as biopolymeric excipients saccharides (Slavin & Carlson, 2014).

I. Background
1.2 Carbohydrates 5

1.2.1 Monosaccharides 1.2.2 Oligosaccharides


These are generally called simple sugars, These yield 210 monosachharides on
and the most common monosaccharide is glu- hydrolysis. On the basis of number of mono-
cose. Most of the monosaccharides comprise of saccharide units present, these are further sub-
the general formula CnH2nOn (Pigman & classified into (Shin & Kim, 2013; Slavin &
Horton, 1972). The different classes of mono- Carlson, 2014): disaccharides (e.g., sucrose,
saccharides include aldoses (functional group maltose, lactose and trehalose), trisaccharides
is aldehyde), and ketoses (functional group is (e.g., raffinose and maltotriose), etc. These can
keto) (Slavin & Carlson, 2014; Werz & exhibit reducing property, when these contain
Seeberger, 2005). On the basis of number of free aldehyde and/or ketone group, which is/
carbon in the sugar, they are also subcategor- are not participated in the formation of
ized into (Shin & Kim, 2013; Slavin & Carlson, linkage.
2014):
1. Trioses (containing three carbon atoms in
the sugar), for example, glyceraldehydes 1.2.3 Polysaccharides
and dihydroacetone, These are formed by uniting monosaccha-
2. Tetroses (containing four carbon atoms in ride or there derivatives. These are joined
the sugar), for example, erythrose and together by glycosidic linkage (Maity et al.,
erythrulose, 2021). Unlike proteins and nucleic acids, poly-
3. Pentoses (containing five carbon atoms in saccharides exist as both linear as well as
the sugar), for example, ribose and xylulose, branched polymers. These are colloidal in
4. Hexoses (containing six carbon atoms in the nature. Polysaccharides are grouped into two
sugar), for example, glucose, glactose, categories (Shin & Kim, 2013; Slavin & Carlson,
fructose and mannose, and 2014):
5. Heptoses (containing seven carbon atoms in
the sugar), for example, sedoheptulose. 1. Homopolysaccharides: These yield one type
of monosaccharides on hydrolysis, for
Physicochemical properties of monosacchar- example, starch, cellulose, glycogen, etc.
ides: These are soluble in water, sweet in taste 2. Heteropolysaccharides: These yield two or
and permeable through plasma membrane. more different type of monosaccharides on
Monosaccharides react with hydrazine to form hydrolysis, for example, hyaluronic acid,
osazones (Pigman & Horton, 1972). They heparin, chondriotin sulfate, etc.
undergo reduction and form sugar alcohols
Some important homopolysaccharides are
(e.g., glucose-sorbitol; fructose-mannitol; galac-
described here:
tose-dulcitol; glyceraldehyde-glycerol, etc.). On
oxidation, these produce sugar acids like glu- 1. Starches—These contain several units of
conic acid. Monosaccharides play varieties of glucose joined in α-1, 4-linkages and are
important physiological functions (Pigman & well-known as examples of
Horton, 1972). These are used for energy pro- homopolysaccharides (Nayak & Pal, 2017).
duction in living organisms. The vital compo- In plants, it is the storage form of
nents of cells are RNA and DNA, which are carbohydrates. Different parts of the plants
composed of ribose and deoxyribose and are are rich in starches like tubers, roots,
well-recognized as the building blocks of life vegetables, cereals, etc. (Nayak & Pal, 2017;
(Minchin & Lodge, 2019). Nayak, Bera, & Hasnain, 2020). In higher

I. Background
6 1. Biological macromolecules: sources, properties, and functions

animals, starches are the most important properties like low density, flexibility, high
source of food. These consist of two types of strength, biocompatibility, biodegradability,
molecules (Fig. 1.1): (A) linear and water etc., which suggest for biomedical
soluble component, e.g., amylose and (B) applications (Hasnain et al., 2020; Kandar
branched water insoluble, e.g., amylopectin. et al., 2021). In traditional healthcare,
Commercially, starch is produced mostly cellulosic biomaterials play an important role
from corn, but wheat starch, potato starch, and recently, some significant areas of
and tapioca starch are also used (Nayak application are being explored with the uses
et al., 2020). of cellulose like drug delivery (Hasnain et al.,
2. Cellulose—It is the chief constituent of 2020; Kandar et al., 2021; Pal et al., 2019b),
fibrous parts of the plants and consequently, tissue engineering (Hasnain, Nayak, Singh, &
is the most abundant organic material Ahmad, 2010; Murizan, Mustafa, Ngadiman,
occurring in nature (Pal et al., 2019b). It is Mohd Yusof, & Idris, 2020), management of
made up of long chains of β D-glucose wound (Alven & Aderibigbe, 2020), etc. By
molecules linked by 1, 4-linkages (Fig. 1.2). It using quaternary ammonium salt the surface
serves as bulk forming agent of the food. of cellulose nanocrystals (CNC) is modified,
Undigested cellulose increases the bulk of which can inhibit the growth of Staphylococcus
feces and helps in the evacuation of bowels. aureus and Escherichia coli (Tavakolian, Jafari,
Cellulose exhibits some of important & van de Ven, 2020).

FIGURE 1.1 Molecular structure of starch: (A) linear and water soluble component: amylose and (B) branched water
insoluble: amylopectin.

I. Background
1.2 Carbohydrates 7
FIGURE 1.2 Molecular
structure of cellulose.

4. Pectins—These form gel with sugar


solutions. In nature, pectins are usually
found in pulps and peels of citrus fruits,
apple pomaces, beet roots, etc. (Nayak &
Pal, 2016a). Chemically pectins are
polysaccharide of galacturonic acid,
galactose, and arabinose (Hasnain et al.,
2020; Kandar et al., 2021). Molecular
structure of pectin is presented in Fig. 1.4.
Pectins have been found to possess
beneficial biological activities, like
antioxidant, antiinflammatory, antibacterial,
immune regulation, and anticoagulation
activities (Rascoń-Chu, Gomez-Rodriguez,
Carvajal-Millan, & Campa-Mada, 2019).
Biomedical applications of pectins include
tissue engineering, drug delivery, wound
FIGURE 1.3 Molecular structure of dextran. healing and gene delivery (Hasnain et al.,
2020; Kandar et al., 2021; Maity et al., 2021;
3. Dextran—It is a highly branched polymer of Nayak et al., 2019, 2021; Rascoń-Chu et al.,
glucose, produced by yeast or bacteria 2019).
(Chen, Huang, & Huang, 2020; Huang & 5. Gum acacia or Gum Arabic—It is a plant-
Huang, 2018). The linear chain dextran derived gum containing hexoses or pentoses
molecular structure are formed by 1, 6-α or both. It is extensively used in
glycosidic linkages (Fig. 1.3). Dextran occurs pharmaceutical, food and cosmetic
in honey, maple syrup, etc. It is used as industries (Nayak, Das, & Maji, 2012). It is
plasma substitutes as it retains water in an effective and useful excipient for the
circulation for longer period, when preparation of nanomaterials for drug
administered intravenously (i.v.). Dextran delivery (De, Nayak, Kundu, Das, &
and its derivatives are being used to Samanta, 2021).
formulate nanocarriers for advanced drug 6. Alginates—These consist of linear polymer
delivery applications (Huang & Huang, of β (1-4)-linked D-mannuronic acid
2018). (M-unit) and α (1-4)-linked L-guluronic

I. Background
8 1. Biological macromolecules: sources, properties, and functions

FIGURE 1.4 Molecular structure of pectin.

FIGURE 1.5 Molecular structure of alginate.

acid (G-unit) (Hasnain et al., 2020; Kandar used in the biomedical applications mainly
et al., 2021; Nayak et al., 2021). Molecular in drug delivery and tissue regeneration
structure of pectin is presented in Fig. 1.5. It (Malakar, Nayak, Jana, & Pal, 2013; Malakar,
is processed from marine algae and giant Nayak, & Das, 2013).
kelp as raw materials. These are widely 7. Chitosan—It is a cationic natured
used as thickener, emulsifier, stabilizer, etc. carbohydrate polysaccharide, extracted by
(Kandar et al., 2021). Alginate based drugs deacetylation of chitin (Hasnain & Nayak,
are effectively used for antimicrobial as well 2018). It is reported to show various
as antiviral therapy (Szekalska, Pucilowska, biological properties including antidiabetic,
Szymańska, Ciosek, & Winnicka, 2016). The antioxidant, immune-enhancing,
alginate film with EDTA exhibited stronger antimicrobial as well as anticancer activities
antimicrobial effects against Gram-negative (Hasnain & Nayak, 2018; Rabea et al., 2003;
bacteria, especially, in case of processed Rı́os et al., 2015). Chitosan is very much
food packaging (Senturk Parreidt, Müller, & effective in the formulation of insulin with
Schmid, 2018). Structural modifications of controlled delivery functionality at the target
alginates can easily be made by using site (Barbosa et al., 2020). Carboxymethyl-
crosslinkers, improvise the mechanical hexanoyl derivative and polyethylene glycol-
strength and cell affinity and was widely trimethyl complexes of chitosan have been

I. Background
1.3 Lipids 9
found to possess fat-lowering and fat- 9. Glycogen—This is also known as animal
preventing properties. Chitosan-based starch, as it is a principal polysaccharide
collagen complex sponges showed occurring in animal tissues, specifically in
effectiveness in the healing of diabetic liver and muscle (Roach, Depaoli-Roach,
wounds (Wang et al., 2008). Chitosan and its Hurley, & Tagliabracci, 2012). Glycogen is
derivatives are being extremely used in many the storage form of energy release, quickly,
biomedical applications, such as drug when needed (Kreitzman, Coxon, & Szaz,
delivery, tissue engineering, wound dressing, 1992). Similar to starch, this is also
orthopedics, etc. (Hasnain et al., 2020; composed of glucose units united by 1, 4-
Hasnain, Ahmad, Chaudhary, Hoda, & linkages and branches arising by 1, 6-
Nayak, 2019; Hasnain, Nayak, Singh, & linkages.
Ahmad, 2010; Kandar, Hasnain, & Nayak,
Sources and functions of various polysac-
2021; Maity, Hasnain, Nayak, & Aminabavi,
charides are listed in Table 1.1.
2021; Nayak, Ahmed, Tabish, & Hasnain,
2019; Pal, Saha, Nayak, & Hasnain, 2019).
8. Agar—It is a natural polysaccharide
obtained from seaweeds. It is a sulfuric acid 1.3 Lipids
ester of a complex galactose polysaccharide
(Kandar et al., 2021). It is nondigestible Lipids are heterogeneous group of organic
material and is used as a bulk laxative. compounds, related either actually or poten-
Recent years, a number of biocompatible tially, to the fatty acids (Pandey & Kohli, 2018).
agar-based composite has been formulated They are poorly soluble in water and soluble in
for their potential applications in biomedical nonpolar solvents like chloroform, benzene,
fields including drug delivery and tissue petroleum ether, etc. In our body, lipids are an
engineering applications (Kandar et al., integral part of the cell membrane structure,
2021; Nayak, Alkahtani, & Hasnain, 2021; metabolic fuel and storage form of energy (van
Shah et al., 2019). Meer et al., 2008; Zheng et al., 2019). Lipids act

TABLE 1.1 Sources and functions of various polysaccharides.


Polysaccharides Source type Functions

Cellulose Plants Cell structure and food additives


Starches Plants Storage and drug adjuvants

Pectins Plants Food additives


Carrageenan Microorganism Food additives
Alginate Microorganism Drug adjuvant
Hyaluronan Animals Animal tissue structure, therapeutic agents
Heparin Animals Animal tissue structure, therapeutic agents
Chondroitin sulfate Animals Animal tissue structure

Chitin and chitosan Animals Tissue scaffolds

I. Background
10 1. Biological macromolecules: sources, properties, and functions

as mechanical, thermal and electrical insulators development of nanocarriers for drug


(Pandey & Kohli, 2018). Lipids are usually clas- delivery (Das, Sen, Maji, Nayak, & Sen,
sified as follows: 2017; Malakar, Sen, Nayak, & Sen, 2012).
c. Cephalins—similar in structure with
lecithin but the base is ethanolamine.
1.3.1 Simple lipids These are found in brain, liver, cardiac
muscles, erythrocytes, etc.
These are esters of fatty acids with certain
d. Plasmalogens—found in brain, cardiac
alcohols, generally glycerol. According to
muscles, erythrocytes, etc.
nature of alcohols, these are (Vance & Vance,
e. Sphingomyelins—on hydrolysis, these
2002):
give a single fatty acid, a nitrogen base
1. Fats and oils: Ester of fatty acids with sphingosine, phosphoric acid and choline
glycerol. These are also known as natural fat but no glycerol. These participate in
or triglyceride or triacylglycerol. At room different signaling pathways.
temperature when these are solid known as 2. Glycolipids: These contain sphingol, a
fat and when liquid these are known as oil. carbohydrate (galactose), and fatty acid.
2. Waxes: These are esters of fatty acid with Large amount of glycolipids are present in
higher molecular weight monohydric the white matter of brain and in the myelin
alcohol. sheath of nerves (Willison, 2018).
3. Sulpholipids: Lipid material containing
sulfur has long been known to be present in
1.3.2 Compound or conjugate lipids the different tissues like liver, kidneys,
brain, etc. It is found in the white matter of
These are ester of fatty acids containing
the brain.
groups, in addition to an alcohol and the fatty
4. Lipoproteins: These are composed of
acids. These are further classified as (Vance &
lipid material bound to the protein. The
Vance, 2002):
lipid of lipoproteins mainly consists of
1. Phospholipids: These contain fatty acids, cholesterol esters and phospholipids (such
glycerol, a phosphoric acid residue and as stearic, palmitic, and oleic acids)
sometimes a nitrogenous base. They are (Schumaker & Adams, 1969). These are
subdivided as: found in plasma and the four important
a. Phosphotidic acids—on hydrolysis, these lipoproteins are chylomicrons, pre-
produce one molecule each of glycerol β-lipoprotein, β-lipoprotein and
and phosphoric acid with two molecules α-lipoprotein. Hyperlipoproteinemia is
of fatty acids. clinically significant, nowadays, as
b. Lecithins—contain glycerol, fatty acid, lipoproteins are directly related with
phosphoric acid and the nitrogen base atherosclerotic cardiovascular disease
choline. These are widely distributed in (Arnao, Tuttolomondo, Daidone, &
different animal tissues including brain, Pinto, 2019).
liver, blood, cardiac muscles, etc., and also
found in plant seeds. Lecithins are used as
emulsifying and smoothing agents in food
1.3.3 Derived lipids
industry (Robert, Couëdelo, Vaysse, &
Michalski, 2020). Lecithins have been These are substances derived by hydrolysis
mentioned to be used for the of simple or compound lipids.

I. Background
1.4 Proteins 11
FIGURE 1.6 (A) Cyclopentano perhydro phe-
nantherene ring system in steroids, and (B) molecu-
lar structure of cholesterol.

1. Steroids: These are abundantly found in carrier systems, such as liposomes, transfero-
nature. Steroids are derivative of complex somes, solid lipid nanoparticles, lipid nanos-
ring system named as cyclopentano tructures, etc.
perhydro phenantherene (Fig. 1.6A). The
important classes of steroids include sterols,
bile acids, sex hormones, adrenal cortical
hormones, Vitamin D, saponins and cardiac
1.4 Proteins
glycosides (Cole, Short, & Hooper, 2019).
Proteins constitute a diverse, heterogeneous
2. Sterols: Cholesterol is a well-known sterol
class of macromolecules and these may be said
(Fig. 1.6B). It is a white and waxy substance,
as the essence of life processes (Zaretsky &
widely distributed in all cells of the body,
Wreschner, 2008; Zhang et al., 2018). These are
particularly in nervous tissue. Cholesterol is
high molecular weight extremely complex
the precursor of bile salts, adrenocorticoids,
polymers of amino acids (Watford & Wu,
sex hormones, Vitamin D and cardiac
2018). In addition to carbon, hydrogen, oxygen
glycosides (Schade, Shey, & Eaton, 2020).
atoms, the molecular structure of proteins con-
Eicosapentaenoic acid (EPA) and
tains nitrogen and sometimes sulfur, phospho-
docosahexaenoic acid (DHA) play important
rus, iron, copper, manganese, iodine, zinc, and
roles with respect to immune functions,
other elements. The amino acids of proteins are
neurological and cardiovascular disorders
joined together with the help of peptide bonds
(Ochi & Tsuchiya, 2018).
(CONH). The common structure of pro-
Basic functions of different lipids are listed tein is presented in Fig. 1.7. These exhibit varie-
in Table 1.2. Recent studies have showed the ties of functions in cells by acting as structural
efficacy of various lipid-based drug delivery materials, carrier molecules, enzymes,

I. Background
12 1. Biological macromolecules: sources, properties, and functions

TABLE 1.2 Basic functions of lipids.


Type of lipids Functions

Fatty acids Precursor of triglyceride and source of energy


Triglyceride Storage of energy, thermal insulation and protection, binding of organs together
Cholesterol Component of cell membranes and also the Precursor of different steroids
Phospholipids Structural component of cell membranes and helps in digestion of fat
Bile acids Helps in fat digestion and absorption of nutrients
Eicosanoids Chemical messenger between cells

Dietary fat Carry lipid soluble Vitamins (A, D, E and K)

FIGURE 1.7 Common structure of protein.

lubricants, etc. (Zaretsky & Wreschner, 2008). are further classified into albumins, globulins,
Proteins derived from different sources (ani- glutelins, prolamins, albuminoids (scleropro-
mals and plants) have been used for the isola- teins), histones and protamines.
tion of peptides, and exhibited different
1. Albumin: These are soluble in water,
biological activities for humans (Daly et al.,
coagulated by heat, and precipitated by
1990; Nayak, 2010). Proteins are classified in
saturated salt solution. Examples are
three groups, namely simple proteins, conju-
lactalbumin, serum albumin, egg albumin,
gated proteins and derived proteins (Watford
myogen of muscle, etc.
& Wu, 2018).
2. Globulin: These are soluble in dilute solution
of strong acids and bases and get coagulated
by heat. Examples are serum globulin,
1.4.1 Simple proteins ovoglobulin, myosin of muscle, etc.
Upon hydrolysis, these types of proteins 3. Glutelin: These are soluble in dilute acids
yield only amino acids or their derivatives and alkalis and get coagulated by heat.
(Murray, Harper, Granner, Mayes, & Rodwell, Examples are glutenin from wheat and
2006; Watford & Wu, 2018). Simple proteins oryzenin from rice, etc.

I. Background
1.4 Proteins 13
4. Prolamines: These are soluble in 70%80% 3. Chromoproteins: These are composed of
alcohol and insoluble in water, absolute simple proteins with chromotropic group as
alcohol and other neutral solvents. prosthetic group. Examples include
Examples are zein (corn), hordein (barley), hemoglobin (prosthetic group is heme),
gliadin (wheat), etc. flavoproteins (prosthetic group is
5. Albuminoids (Screlroproteins): Albuminoids riboflavin), cytochrome (prosthetic group is
are insoluble proteins and form supportive heme), etc.
tissues. These are animal proteins found in 4. Phosphoproteins: These are composed of
hair, nails, horns and hooves. Examples are proteins and phosphoric acid as the
keratin, collagen, gelatin, etc. prosthetic group. Caesin (milk protein) and
6. Histones: These are soluble in water, very vitelline (egg yolk protein) are the important
dilute acids and salt solutions. These are not examples of this group.
conjugated by heat and contain basic amino 5. Lipoproteins: These proteins are the
acids. Examples include nucleic acids. combination of proteins and lipids (fatty
7. Protamines: These are the simplest of acid, lecithin, cephalin, etc.) as prothetic
proteins and are basic polypeptides, soluble group. Lipoproteins occur in blood, cell
in water and ammonium hydroxides. These nuclei, milk, cell membranes, egg yolk, etc.
are not conjugated by heat. Examples 6. Metalloproteins: These are compounds of
include salmine (salmon sperm), clupeine proteins and some metals (such as iron,
(herring sperm), etc. cobalt, zinc, manganese, copper and
magnesium). Examples are ferritin,
ceruloplastin, carbonic anhydrase, etc.
1.4.2 Conjugated proteins
These contain simple protein combined with
1.4.3 Derived proteins
nonprotein prosthetic group (Murray et al.,
2006). These include: (1) nucleoproteins (2) pro- These are formed from simple and conjugate
teoglycans and glycoproteins (3) chromopro- proteins by denaturation or partial hydrolysis
teins (4) phosphoproteins (5) lipoproteins and (Murray et al., 2006). They are of two types (1)
(6) metalloproteins (Murray et al., 2006; denatured or primary derived proteins and (2)
Watford & Wu, 2018). secondary derived proteins (Murray et al.,
2006; Watford & Wu, 2018).
1. Nucleoproteins: These proteins are
composed of simple proteins with nucleic 1. Denatured or primary derived proteins:
acids as prosthetic group. In nucleoproteins, These proteins may be of different types.
protein moiety is usually a basic protein like a. Proteans—derived in the early stages of
protamine and histone. Examples include protein hydrolysis by water, dilute acids
chromosomal proteins and some glandular or alkalis or enzymes. Examples include
proteins. fibrin from fibrinogen, myosan from
2. Proteoglycans and glycoproteins: These myosin and edestan from edestin.
proteins contain carbohydrates as prosthetic b. Metaproteins—derived by further
group like hyaluronic acid and chondroitin hydrolysis by stronger acids or alkalies,
sulpahte. These are mainly found in blood which are insoluble in very dilute acids
plasma, gastric and salivary mucine, and alkalis. Examples of such proteins
immunoglobulins, human chorionic include acid metaproteins and alkali
gonadotropins, etc. metaproteins.

I. Background
14 1. Biological macromolecules: sources, properties, and functions

c. Coagulated proteins—derived by the Bioactive proteins obtained from legumes have


action of heat, ultraviolet (UV)-rays, X- been found beneficial in the prevention of obe-
rays, very high pressure, mechanical sity and type-II diabetes (Moreno-Valdespino,
shaking, etc. Examples are coagulated Luna-Vital, Camacho-Ruiz, & Mojica, 2020).
albumin, cooked meat, etc. Anticancer activities are also demonstrated by
2. Secondary derived proteins: Progressive some important biological proteins like lectins,
hydrolysis of peptide bond caused glycoproteins, etc. (Laaf, Bojarová, Pelantová,
breakdown of proteins into smaller Křen, & Elling, 2017; Rodrigues Mantuano
molecules, which include (Murray et al., et al., 2020; Singh, Kaur, & Kanwar, 2016).
2006): Gelatin obtained from animal collagen, either
a. Proteoses—formed by the action of acid or alkali treated, is used in bone tissue
pepsin and trypsin, engineering as it is biocompatible, low immu-
b. Peptones—produced by further nogenic and biodegradable (Hasnain et al.,
hydrolytic decomposition and 2019). Pharmacological effects of bioactive pro-
c. Peptides—composed of two or more teins/peptides along with their sources are
amino acids (such as dipeptides, and listed in Table 1.3.
polypeptides).
Plethora of proteins and peptides with vari-
eties of biological activities has already been 1.5 Nucleic acids
identified (Nayak, 2010). Some of the proteins
and peptides exhibit bioactivities like antioxi- Nucleic acids are nonprotein nitrogenous
dant, antihypertensive, antibiotics, immuno- macromolecules, in which the nucleotides
modulatory, anticancer activities, etc. remain linked to each other by phosphodiester
(Giromini, Cheli, Rebucci, & Baldi, 2019). bonds in-between the 30 and 50 position of the

TABLE 1.3 Pharmacological effects of bioactive proteins/peptides along with their sources.
Bioactive proteins/
peptides Sources Pharmacological effects

Fibrinolytic Eisenia fetida Antitumor activity against several hepatoma cell lines, in vitro and in vivo (Chen
enzymes (earthworm) et al., 2007)
Hirudin Hirudo Anticoagulation activity through inhibition of thrombin activity (Markwardt, 2002)
medicinalis
Cordymin Cordyceps Antifungal activity (Wong et al., 2011), anticancer and inhibitory effect on HIV-1
militaris reverse transcriptase (Wong et al., 2019), antiinflammatory and antinociceptive
activities (Qian, Pan, & Guo, 2012)
Lectin Cordyceps Hemagglutinating activity and mitogenic activity (Wong, Wang, & Ng, 2009)
militaris
Ginkbilobin Ginkgo biloba Antifungal activity (Wang & Ng, 2000)
seeds
Dioscorin Dioscorea batatas Trypsin inhibitory activities (Hou et al., 1999)
Trichosanthin Trichosanthes Anti-HIV activity (Zhao, Ben, & Wu, 1999) and antiviral activity against hepatitis B
kirilowii virus (Wen et al., 2015)

I. Background
Another random document with
no related content on Scribd:
Courtesy Assoc. First Nat’l Exhibitors, Inc.
A Tête-à-Tête With a Lion.
Note that the lioness is looking not at the actress opposite her, but at the
motion-picture camera that annoys her with its clicking.
Courtesy Assoc. First Nat’l Exhibitors, Inc.
Acting With a “Tame” Lion.
There is always enough danger in playing “opposite” a lion to make it easy
for any actor to “register fear.” Note how the lion is baring his teeth.

There, in a nutshell, is one of the big difficulties that anybody who


wants to help along the moving-picture industry, either by making
better pictures or by encouraging better pictures, is up against.
Between the public on the one side and the big distributors and
producers on the other side stand the exhibitors, who must be “sold”
on a money-making basis, before any great change can come about.
In the long run, to be sure, audience value counts. In the long run
you and Andrew McGinnis and George Lenox and Fuller Westcott
have to be satisfied with the pictures you see, or you will quit going
to see what your local exhibitor-man has to offer. But remember,
that’s in the long run.
Now, with this explanation of what a good picture has to overcome
to find its way into the movie palaces, let us see how good it can be,
and still “get by.”
First, it must be good enough to make an impression on the
distributors who buy it from the producer and sell it to the movie-
theater owners who exhibit it. They must think, at least, that it is
good. And to make them think that, it has got to have good selling-
points such as were suggested a little way back, so that they can
brag about it to the exhibitors and make the re-selling or renting of
the prints easy.
Second, it must be good enough so that when the exhibitor sees it,
he will decide that his audiences will like it—or at least that enough
people will like it to more than compensate him for the price he has
to pay in rentals.
Third, it must be good enough to satisfy the people who pay to get
in to see the show, or they will be apt to stay away next time, so that
in the end the exhibitor will lose money unless he shows better films.
And in each one of these cases it mustn’t be too good, or at least
too good in a “highbrow” sense.
It must have enough popular appeal, so that, collectively, millions
of people will like it, in order to make it profitable for the exhibitor,
and the distributor, and the producer.
A picture was made in England from a story by Sir James Barrie,
who wrote “Sentimental Tommy” and so many other fine books and
plays. It was called “The Will.” It showed an old firm of lawyers in
London, and a young couple that came to the office to be married.
There was a “Little black spot” in the character of the young groom—
a streak of mean selfishness. Throughout the lifetime of that couple it
grew and grew, because it wasn’t weeded out, until in the end it
made them both very unhappy, and even spoiled all their children’s
lives. When he was a very old man, the fellow who was married at
the beginning of the picture came back to the old lawyer’s office to
make his will, and admitted that he had spoiled his life, and the lives
of all those about him, through his failures to weed out “The little
black spot” in time.
You can see how different that picture is from most of those that
you see, month after month, at your nearest movie-house. For one
thing, it didn’t have any particular love-story, which more people like
to see than anything else. For another thing, it has a sort of unhappy
ending, which, in this country, relatively few people like to see. So,
although the picture was beautifully produced, and although it was
interesting as it went along and pointed a big moral quite without
being “preachy,” no one bought it for this country. It was sent back to
England. The distributors, who could have bought it for a song
compared to what they have to pay for even the poorest pictures that
are made here in America, were afraid of it, because they felt it
would be hard to sell to exhibitors, who wouldn’t think enough people
in their audiences would like it to make it profitable.
Think a moment. Would you have liked it, just because it was a
worth-while story, beautifully produced? Would you have liked it even
though it had no particular love-story, and no thrilling adventure, and
no particularly unusual scenes, and did have an unhappy ending?
You would have admired it, undoubtedly, if you had seen it, and
admitted it was good; but you wouldn’t have liked it particularly.
Courtesy Universal Pictures Corporation.
An Elephant on a Rampage.
When animal pictures are being taken there is always a chance for things to
go wrong. Animals almost always seem to be irritated by the clicking of the
camera.
Courtesy Universal Pictures Corporation.
Human Brains Against Brute Strength.
Whenever possible, scenes that “go wrong” are turned to account. This
entire episode was photographed and eventually used in a “nature” film.

It was too good a picture for the American market, at this stage.
On the other hand, if a picture has certain fundamental points of
popular appeal, a romantic love-story or a thrilling climax or a
wonderful setting of unusual beauty or charm, and good selling-
points as well, such as a famous author or a great star, it can be just
as good as anybody is able to make it. Under those circumstances it
cannot be too good. Look at the best Griffith pictures, or the best
Rex Ingram pictures, or the best pictures that Douglas Fairbanks has
made, like “Robin Hood,” or the best that Mary Pickford has made, or
Charles Chaplin, or Harold Lloyd.
So far, there has been one great stumbling-block in the way of
better pictures. It has even affected such great producers as Griffith
and Ingram. They have been afraid of doing the very best they were
capable of, for fear of being “too good.” They were afraid of being
“over the heads” of too many people in the audience. They were
afraid of not having enough “popular appeal.”
That is why, in “Way Down East” Griffith stooped to cheap “slap-
stick” comedy that was really beneath, and incidentally really less
funny than, what he might have done. It was why Rex Ingram, in
“Turn to the Right” made a picture that was about down to the level
of an eight-year-old child, in spite of its beautiful production. It was
why such pictures as Universal’s “Merry-go-’Round” drop to cheap
and overdrawn sentimentality in places, instead of sticking to the real
thing.
The danger with distributors and exhibitors as well as producers, is
that they are afraid of losing money on pictures that are “too good.”
What they are afraid of is a real danger: it is true that pictures may
be “too good.” That is, not interesting enough in a popular sense, in
spite of their artistic excellence.
If only producers and distributors and exhibitors could all get
pictures that were just as good as they could possibly be without
being “too good,” we’d be all right.
It’s safer, though, from a money standpoint, to have pictures a little
below than a little above the line that marks the limit of popular
appreciation. At least, for a while.
There we have the whole problem of how to get better pictures:
daring to keep right on the border line of popular taste, without trying
to play too safe by sagging away down below it, in an effort to appeal
to greater numbers of people.
There’s a curious thing about this problem. Great numbers of
people will keep away from pictures that seem to them too
“highbrow” to be interesting. But on the other hand, unless pictures
are good enough to keep people feeling that they are getting
something worth-while, after a while they will stop going to that kind,
also.
Have you ever played tennis with a man you could always beat? If
you did, you found that after a while it wasn’t half so interesting as
playing with a man who could give you a rattling good game, and
whom, if you were at your very best, you might beat. For some
reason there is a great stimulus in progress; we like to play tennis
best with people who are so good that to play with them means
continually improving our own game.
Nobody would ever think of going to school if the teachers didn’t
know more than their pupils. That would be worse than forever
playing tennis with a man who could never hope to ever equal your
own game.
Do you see what we are getting to? Leadership!
Motion pictures, are, in a certain sense, a part of the great
publishing business of the United States. They publish stories in
picture form. And in those stories they publish ideas, and ideals, and
rules of conduct, and good taste, and good sense,—or the lack of all
those things.
It is through the publishing business—the movies as well as books
or magazines or newspapers—that we get the information and ideals
by which we live. The publishing business is the main channel, aside
from schools and conversation and churches, through which we get
the information and ideas that enable us to make progress, that
enable us to get ahead.
Accordingly, the publishing business—and the movies with the rest
—has to have in it the element of leadership.
It’s as though we were going to school when we go to see motion
pictures. In a sense, we are. And just as, if we really were not
learning anything there, we wouldn’t go to school, so, with motion
pictures, if we don’t find anything worth while in them, after a while
we get tired of them and lose interest, and stop paying money to
watch them.
In one year, when motion pictures got too far below the line of
popular appreciation, enough people stopped going to them to drop
the total box office receipts in the country more than a hundred
million dollars.
So, while for a time there is more money in playing the public
down than there is in playing it up (since more people come, at first
at least, to see pictures that are too cheap for their taste, than come
to see pictures that are a little too good for their taste), in the long
run, playing the public up pays best.
In other words, if the leadership element is present at a motion
picture, if it is a picture that is thoroughly worth while, and yet is not
too good to “get across,” it will both make money and build business,
while a cheap sensational picture, though it may make more money
than a better film at the time it is released, will in the end lose
business for the firm producing it, because in the long run it drives
away business instead of bringing it in.
When you go to see pictures, look for something worth while. If
you find it, particularly in a picture that you like very well, don’t be
afraid to let the local exhibitor or theater manager in charge of the
movie-palace where you saw the show know that you liked it and
thought it was good.
That will help him just that much in deciding what kind of pictures
his audience likes.
Remember; while a picture must be financially profitable for the
producer, and so can’t be above popular appreciation, it still must be
good enough to be right at the upper edge of that popular
appreciation, and trying to push it always a little bit higher.
Courtesy United Artists Corporation.
One of the Big Scenes in “Robin Hood.”
While it usually costs an enormous amount to film the so-called big “mob”
scenes in elaborate productions, they are often very effective. Notice how
well trained the “extras” are here.
Courtesy Assoc. First Nat’l Exhibitors, Inc.
Spending Money on a “Spectacle.”
It used to be thought that “great” pictures could be made by unlimited
expenditure in “mob” scenes and “big sets.” This scene, however, is from
one of the films that helped disprove it; costing nearly half a million, it
proved to be a comparative failure.
CHAPTER IX
AMERICAN MOVIES ABROAD

Have you ever happened to think: the world has at last found a
universal language!
The men who created Esperanto, or any of the other so-called
“universal” languages, little imagined that before their product even
reached its twenty-fifth birthday the old world would have
unconsciously accepted an entirely new method of interchanging
ideas—and that the “new” method would be the oldest language of
all. “Say it with pictures.”
Long before the Romans began to roam—even before the
Athenians settled down in Greece—men talked to each other in
pictures. The Eskimos scratched their tales on bone, and the
Egyptians carved pictures of eagles and lions into solid rock, and
from such crude beginnings, little by little, the various languages
evolved.
Now, we have a chance, in a way, to go back to the beginning,
without losing the later developments.
The human face is a document that all may read. An expression of
sorrow is not confined to any one language. A smile goes round the
world. Fear—anger—hope—excitement—can readily be recognized,
whether the face that expresses them is white or black, man or
woman or child, long or thin, or round and slant-eyed.
A boy laughing in Southern California may make a Hindu in India
smile in sympathy, when that laugh appears upon a Bombay screen.
Tears are universal. So is a grin.
Motion pictures made in one country may be shown in any other,
and find appreciation. Films produced in America may go to all the
countries of the world, and do.
But America is not the only country producing motion pictures.
French films or German, or Italian, or English, or Scandinavian, or
any other, may also be shown in any of the countries of the globe,
including America.
To be sure, there are changes that have to be made, here and
there. The leaders or captions—now usually called titles in this
country—have to be translated into the required language;
sometimes the action in the pictures has to be cut to meet the
requirements of differing customs and conventions. And the
audiences of the globe do not all like the same things, or see them in
the same way.
A missionary returning from one of the island groups in the South
Seas recently told me of the first “movie-palace” to be established in
his vicinity. “Shows” were given only at irregular intervals, and were
talked of for days in advance, and attended like country fairs, by all
the villagers able to walk, from miles around.
As the job of translating the titles on the film into the native dialect
would be altogether too expensive for such limited audiences, a
native interpreter, able to guess at the meaning of the foreign titles
here and there, stood in front of the screen and told the story as he
imagined it ought to be, as it flickered along. The highly emotional
audience was always greatly excited, and the enthusiasm and
shouts of the natives gradually grew louder and louder, as the action
progressed, often drowning out altogether the shouted explanations
of the interpreter. Not infrequently the excitement grew almost into
hysteria, so that it was nothing unusual for the show to wind up in a
free-for-all fight.
But the most interesting thing was the attitude of the native
audience toward the characters of the photoplay.
Their virtues were not the civilized virtues, nor were their vices
those of the film producers, so that they saw the hero as a good-for-
nothing, and the villain, often enough, as a hero. When the
melodramatic “heavy” pulled out his knife and plunged it into the
trusty guard, they cheered him on, and when he next dragged the
beautiful heroine into his refuge in the hills by the hair of her head,
they were more enthusiastic still. But when the hero appeared on the
scene in the nick of time, to help the girl escape and foil the villain’s
plans, they hissed like good fellows, and nearly broke up the show.
Let us see for a moment just what the world market in motion
pictures means to America.
Not in dollars and cents, because, alone, the money side of the
picture industry is neither exceptionally important nor particularly
interesting. The film industry is now, I believe, the fifth largest in the
country, and its exports and imports run to millions of dollars
annually. American pictures for the whole world would mean more
dollars coming our way, and more prosperity in this country; but that
is neither more nor less than can be said of half a dozen other
industries. Money is not the only thing we need to make America the
greatest country in the world.
Indirectly, the movies mean more, even from the money
standpoint, than the tremendous direct returns from the industry itself
give any idea of. The citizens of Rio de Janeiro, let us say, watch
American films and become acquainted with the interiors of
American rooms, American furniture and all the rest. When they
have to furnish a home of their own those Brazilians have to choose,
let us say, between German-made furniture and American. If they’re
already accustomed to the American designs and styles, through
seeing them on the screen, they will take them, unhesitatingly, in
preference to the German. For what people have already accepted
unconsciously as a standard—what they see others using in
countries they look up to—inevitably appeals to them for their own
use. And as with furniture, so with all the host of other things
American, manufactured for export as well as home use.
The really big thing about American films abroad—in Europe, in
Asia, in Africa and South America—is that they carry American
ideas, and American ideals and American influence, around the
world.
To-day the American girl is known all over the globe. The faces of
our screen actresses—Mary Pickford, Constance Talmadge, Lillian
Gish, and many more—are watched in Calcutta and Petrograd,
Cape Town and Budapest.
Doesn’t that make it seem a fortunate thing that Mary Pickford,
with her charming smile, has come at least as near as she has to
representing the real heart of America—all that is cleanest and
kindest and best in us? For, when all is said and done, she more
truly, perhaps, than any other one living person represents America
in foreign lands.
And on the other hand, doesn’t it seem a pity, and more than a pity
—yes, a great misfortune, a terrible calamity—that so many films,
made by commercial-minded producers with apparently no spark of
the real spirit of service or patriotism, go forth across the face of the
world and spread abroad their idiocies, and meannesses, and lack of
idealism, and even uncleannesses, as representatives of America?
Think of that, next time you happen to pay money to watch a
worthless movie; it may be representing America abroad!
To-day the country that sends its films into foreign lands is leading
the thought of the world.
It is probably not too much to say, although the bare thought itself
is a staggering one, that to-morrow the country that excels in the
production of popular motion pictures will dominate the world.
Fortunately, in the early days of the picture industry in this country
there was a man known as David Griffith, who was something of an
actor, a little of a writer, and possessed no small measure of real
power as a story-teller.
From the very start, the mechanical and inventive end, as well as
the commercial and organization end, of the industry in this country
outstripped competition. Combined with Griffith’s story-telling ability,
this technical supremacy and commercial organization put American
films in front of those produced elsewhere.
American movie-palaces mushroomed into existence by the
hundreds, and we developed a huge domestic market that made
possible extravagant spectacle-productions costing first tens of
thousands, then hundreds of thousands of dollars. The name of
David Wark Griffith became known all over the world; the supremacy
of American films became everywhere acknowledged; pictures from
the United States went to every corner of the globe, carrying
American prestige and influence, increasing American commercial
prosperity and development.
When the World War ended—and though this may seem so
exaggerated that it sounds like a joke, it is not—no little degree of
America’s influence and predominant position, during the early
weeks of the Peace Conference at Paris, was due to the fact that
through the preceding decade our pictures had circled the world.
But that is not the end of the story. Since then there has been a
big change.
Even Griffith, for that matter, as a leader of American picture-
makers, has by no means been universally popular outside this
country, although as a whole his pictures have received almost as
great acclaim as they have here.
Once, for instance, the popularity of his films induced one of the
foreign agents to pay some thousands of dollars for the “Far
Eastern” rights on “Intolerance”—including China and Japan. The
Chinese did not think much of it, and the distributor lost money. But
in Japan the exhibitors were smarter. Having secured the picture
“sight unseen” for the Islands, they had to play it to get their money
back. But they felt, after seeing it, that possibly their Japanese
audiences would not particularly care for it—so they prepared
carefully an exploitation campaign worthy of the best advertising
brains in this country. “Intolerance,” they said, was at once so artistic
that it appealed to the highest intelligence, and so simple that any
man of good sense could appreciate it. To fail to be moved by its
beauty and artistry would mark anybody as being—well, stupid.
“Intolerance” was a great picture, but it was too long, and too hard
to follow, for the average Japanese audience. The Japanese did not
really like it any better than the Chinese did, but because of the
clever advertising beforehand, each person who was bored by the
big foreign film was slow to admit it, because of the fear of labeling
himself stupid. Many people praised the picture, whether they liked it
or not, to show how wise and clever and cultured and intelligent they
were. So “Intolerance” made money in Japan. But then, too many
people who had seen it began comparing notes, and found that it
really was possible to have what passed for good sense, and yet not
like that particular film.
Since nobody likes to be laughed at, there wasn’t any great fuss
made about the matter one way or the other, but I am told that the
word “Intolerance” has been incorporated into the slang (if we can
call it that) of the Japanese language; when a man stretches the
truth too far, or tried to “put on too much dog,” as they might say in
Arizona, his Japanese companions merely smile and perhaps shrug
their shoulders a trifle, and murmur “Intolerance.”
The fact is, American films, from the very start, have lacked the
inner value, the idealism, the spiritual vision and far-sightedness that
make for real leadership. The result is that at the present time films
from half a dozen countries are competing successfully with ours,
and to a considerable extent driving them from the foreign field.
In Germany, after the War started, the making of motion pictures
developed as plants might in an enclosed garden. Shut off from the
rest of the world, and the influence in particular of American motion-
picture methods, Germany developed methods of her own. Chief of
all these was the tendency to tell the story for the sake of the story
itself, with a real story-teller, the dramatic author, in full charge of the
production. Of course this has not always been the case, nor has it
been particularly evident, but on the whole it has meant a great deal.
It meant that the author brains, instead of the glorified director
brains, or the irresponsible star brains, have been the predominating
influence in the pictures.
Over here it has been Charles Ray or Bill Hart, Lasky or Ince,
deMille or Neilan. Only comparatively recently, largely through the
Goldwyn organization, have authors—Rex Beach, and Mary Roberts
Rinehart, and Rupert Hughes, and so on—come into any particular
prominence or influence in picture making.
The result of this has been that our films have been too highly
commercialized. The making of movies is of necessity very largely a
commercial proposition, but here it has been overdone.
Since the very first, Griffith has remained almost the only one of
our real story-telling producer-directors who has put individuality and
authorship above the box-office returns. Even he doesn’t do it
consciously; he tries, I suppose, to make pictures, as all the rest do,
that will attract the largest audiences. But he has ideas and
prejudices and opinions of his own—the things that make for
individuality and leadership—and he would rather lose every dollar
he has ever made than give them up.
While abroad the work is commercialized, too, just as ours is,
there is a little more vision in it, and in some ways the films are
better.
“Gypsy Blood,” “Deception,” “The Golem,” the “Cabinet of Dr.
Caligari,” “Our Mutual Friend,” “Carnival,” “I Accuse,” “Theodora,”
“Hamlet,” “Peter the Great,” and a good many more have made
tremendous records for themselves in this country. German,
Norwegian, French, Italian, English.
Almost as if in reply, Douglas Fairbanks and Griffith made
respectively “Robin Hood” and “Orphans of the Storm.” They gave us
a good chance to compare our best home product with the foreign-
made article.
The Fairbanks and Griffith pictures show that we can at least
equal the German and other foreign films, if we try. Both these
American pictures have a pictorial beauty that no foreign picture has
ever equaled. The Fairbanks film has a suspense, and the Griffith
picture both feeling and excitement, that no picture made outside of
this country has ever shown.
So, we can lead the world, if we will. But unfortunately, those two
pictures are exceptions. One can name a few more, like “Little Lord
Fauntleroy,” “Humoresque,” and “Over the Hill,” that are good
enough to hold their own with the best producers elsewhere; but that
is about all. The run of our American-made pictures are not good
enough, to-day, to deserve world supremacy.
That is something to think about.
The German pictures, as well as those of some of the other
foreign countries, have certain qualities, resulting from an
unwillingness to compromise with ideals, that allow them, as a class,
to outrank ours. For instance, while the Germans desire beauty, just
as we do, and would like to have their heroine as beautiful as ours,
they also desire a real ability to act. If they can not have both, they
will let the beauty go, and take the real acting. We will not; we let the
ability go, and stick to the pretty flappers. Accordingly, in American
pictures, our leading actors and actresses are almost always good-
looking—and frequently poor at acting.
It is the same about truth, or the sense of reality. We sacrifice
convincingness—fidelity to life—truth—to our desire for youth and
beauty. If we could have both, well and good; but it is impossible.
Accordingly, on the American screen, we see, again and again, our
beautiful little flapper friends playing parts that should be taken by
older women—not so young and pretty, perhaps, but true to life,
instead of childish caricatures of truth.
Even with Griffith’s “Orphans of the Storm,” we see still another
sacrifice of an ideal—one might almost say principle. That is the
giving up of historical value, and big things, for excitement, and little
things. The French Revolution is a tremendous story in itself; in the
foreign made films it is made the backbone of the whole story; in
Griffith’s film, it is merely a background, while the “main” story is
centered about one or two appealing characters, that mean, except
for momentary entertainment, little or nothing. It is a question of
Lillian and Dorothy Gish being more important, on this side of the
Atlantic, than the French Revolution; but on the other side, when the
French Revolution is filmed, it is more important than the great
actress who plays in the picture—Pola Negri.
Also, in the mad “run to the rescue” in “Orphans of the Storm,” the
main dramatic value of the story is sacrificed in order to have the
mechanically produced excitement of horses galloping across Paris
in time to save the beautiful Lillian from the guillotine. And who leads
the headlong, melodramatic dash across the city? Why, Danton
himself, leader of the Revolution! That’s putting it on pretty thick!
There is the whole trouble with our American pictures: in a single
sentence they are willing to sacrifice too much, to “tell a good story.”
For with our producers the “good story” means really the entertaining
or exciting or pretty story, which is in the last analysis the most
popular story instead of the really best story.
Roast beef and oatmeal are a better diet, in the long run, than
candy. Candy tastes better, perhaps, for the moment, and more
people will buy it—but in the end, too much of it makes you sick.
Our American motion-picture producers are specializing on candy,
because—for the moment—more people want it. But they’re over-
doing the thing. If they want to hold the world leadership in movie-
making, they must turn out more roast beef.
And we must help them, you and I, by demanding something in
pictures besides candy, and in learning to like and applaud the really
worth-while films that we can turn out, when they come along.

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