Biomaterials

(MME414A)

Session 2020-24

Submitted to:
Dr. Muhammad Asif Hussain

Submitted by:
Sehar Khalid (20MME-S1-304)
Maroof Faheem (20MME-S1-313)
Muhammad Nauman Butt(20MME-S1-315)

Institute of Metallurgy and Materials Engineering

Faculty of Chemical and Materials Engineering
University of the Punjab Lahore
Biomaterials
Assignment

Table of Contents
1. Role of Biomaterials in Controlled Drug delivery systems:.................................................................................3
1.1. Stimuli-responsive Biomaterials:.......................................................................................................................... 3
2. Drug Delivery systems and their types:........................................................................................................................4
2.1. Conventional drug delivery systems:...................................................................................................................4
2.2. Controlled drug delivery systems:........................................................................................................................ 4
3. Conventional vs. Controlled Drug Delivery Systems:..............................................................................................5
3.1. Advantages and limitations of Conventional DDS:.........................................................................................6
3.2. Advantages and limitations of Controlled DDS:..............................................................................................6
4. Advancements in biomaterials in CRDDS:................................................................................................................... 6
4.1. CRISPR CAS9 Based Systems:.................................................................................................................................. 7
4.2. Microfluidics in Controlled Drug Delivery:........................................................................................................7
4.3. Molecularly Imprinted Polymers (MIPs):.......................................................................................................... 7
4.4. Quantum sensing Drug delivery:........................................................................................................................... 7
5. Conclusion:................................................................................................................................................................................ 8
References........................................................................................................................................................................................... 9

List of Figures

Figure 1 A typical bolus of (a) Conventional DDS (b) Controlled DDS 4

Figure 2 Plasma drug levels with time after administering (a) Single conventional dose, (b) Multiple
doses, (c) Increased single dose................................................................................................................................................. 5
Figure 3 Molecular Imprinting polymers synthesis protocol.......................................................................................7

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Biomaterials
Assignment

Assignment
“Examine the role of biomaterials in controlled drug
delivery systems."
1. Role of Biomaterials in Controlled Drug delivery systems:
Biomaterials play a critical role in drug delivery through the modulation of drug pharmacokinetics.
They are designed to interact optimally with biological systems to dictate the properties of a drug
delivery system to a significant extent. Biomaterials range from polymers and polysaccharides to
proteins, lipids, and peptides, and they can be optimized for various drug delivery system scales as
well as routes. Some of the factors considered include biodegradability, biocompatibility, non-toxicity,
mechanical strength, mucoadhesive-ness, and hydrophilicity. In most cases, biodegradable polymers
are preferred because they do not create toxic residues in the event of residue accumulation. Although
most non-biodegradable systems have similar capacities, they may form the basis for the development
of disintegration strategies. These aspects form the basis of encapsulation, targeted delivery,
controlled release, biocompatibility, and biodegradability in DDS factors and subsequently
influence therapeutic potency while minimizing adverse outcomes. [1]

1.1. Stimuli-responsive Biomaterials:

Responsive biomaterials, also known as smart polymers, change their behavior in response to external
factors, either physical or chemical, which is useful in drug delivery systems. These polymers have
been essential in creating nanomedicines by controlling how the cargo is released. They can be
classified as either responding to a single stimulus or multiple stimuli, triggered by external (e.g.,
temperature, electricity) or internal factors (e.g., enzyme levels, pH). Strategies for controlling drug
release include activating nanocarriers and encouraging polymer uptake by target cells. This dynamic
interaction between biomaterials and drug delivery systems highlights their crucial role in precisely
delivering therapeutic treatments. These systems can release drugs when triggered by changes in
temperature, pH, solvent, ultrasound, electric or magnetic fields. For example, pH-responsive materials
can deliver drugs to specific organs or tissues based on their pH levels, enabling targeted drug
delivery. Similarly, redox-responsive materials can release drugs inside cells, especially in cancer
treatment, by exploiting differences in tissue redox potential. Enzyme-responsive systems use specific
enzymes to trigger drug release, which can be particularly effective in areas of inflammation. Physical
stimuli like light, heat, electricity, magnetism, and ultrasound waves can also be used to enhance
controlled drug release, making targeted therapy more precise and less invasive. These innovative
drug delivery systems hold great promise for tailoring treatments to diverse medical needs. [1]

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Biomaterials
Assignment

2. Drug Delivery systems and their types:

FDA1-recognized drug APIs treat diseases; drug delivery enhances therapeutic efficacy by targeting
specific body regions with medication concentration. Drug delivery is a technique of delivering
medication to a patient in such a manner that specifically increases the drug concentration in some
parts of the body as compared to others. [2]

There are two types of Drug delivery systems: conventional drug delivery systems and controlled
drug delivery systems.

2.1. Conventional drug delivery systems:

The conventional drug delivery systems include methods such as tablets, capsules, and ointments
that are integrated with drugs in bulk, micro, or nanoforms for administration through various
routes like oral, buccal, rectal, subcutaneous, intranasal, intramuscular, intravenous,
pulmonary, and transdermal. In this system, dosage forms can be in the form solids, semisolids, and
liquid. Solids dosage forms includes tablets, capsules, Sublingual and Buccal tablets, Capsules,
Lozenges, Pills and Granules. Semisolids dosage forms include ointments, transdermal patches, pastes,
lotion, creams, and gels. Liquid dosage form includes oral solutions, emulsions, syrups, elixir 2, drops
and mouthwashes. These conventional DDS uses immediate release of drug followed by absorption of
drugs, in the forms of different drug dosage design as previously discussed, through various routes. [2]

2.2. Controlled drug delivery systems:

In Controlled drug delivery method maintains a consistent drug level in the body over time. Figure 20
illustrates the plasma concentration versus time Pharmacokinetics (PK) curves for conventional and
controlled delivery systems. Conventional systems exhibit fluctuating drug levels with multiple doses,
while controlled systems maintain steady drug levels with a single dose, ensuring therapeutic
effectiveness as shown in the figure (1). [3]

Figure 1 A typical bolus of (a) Conventional DDS (b) Controlled DDS

The rationale behind controlled drug delivery systems is to minimize dosing frequency, blood plasma
level fluctuations, enhance patient compliance, reduce adverse effects, and lower drug toxicity. Unlike

1
FDA stands for food and drug Administration, agency in United states of America.
2
Elixir: oral liquid with ethanol/sucrose, antimicrobial preservatives, masks taste of drugs, pleasant Flavors.

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Biomaterials
Assignment
immediate release systems or conventional DDS, where drug availability depends on absorption
physiology, controlled delivery systems rely on dosage for drug administration rate. These systems
aim to reduce dosing frequency by incorporating loading and maintenance doses. The loading dose
ensures a rapid onset of pharmacological effect, while the maintenance dose maintains a steady drug
concentration over time, following zero-order kinetics. [4] [3]

Controlled release drug delivery systems are categorized according to the mechanism of drug release
from the dosage form, including dissolution-controlled, diffusion-controlled, water penetration-
controlled (such as osmotic pressure-controlled and swelling-controlled), chemically controlled,
and nanoparticle-based systems. [3] [4]

3. Conventional vs. Controlled Drug Delivery Systems:

Conventional drug delivery systems, such as tablets, capsules, and syrups, are rapidly cleared from the
body, leading to inconsistent drug levels. Upon ingestion, drug levels spike before rapidly declining,
often falling below therapeutic thresholds. This rapid fluctuation may result in inadequate therapeutic
responses. To maintain drug concentrations within the therapeutic range, various strategies have been
explored. While administering multiple doses may appear as a solution, it often leads to erratic drug
levels, compromising efficacy and safety. Additionally, delivering a single large dose can cause
unintended adverse effects. Controlled release drug delivery systems are thus essential to sustain
stable drug levels within the therapeutic range over an extended period. Hence, controlled release DDS
are required to maintain the plasma drug levels at a constant rate within the therapeutic window and
offer the desired therapeutic effect for a longer duration of time. [3]

Figure 2 Plasma drug levels with time after administering (a) Single conventional dose, (b) Multiple doses, (c) Increased single dose.

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Biomaterials
Assignment

3.1. Advantages and limitations of Conventional DDS:

Conventional DDS despite their dosage form design and their responsiveness through various routes
of administration have advantages and limitations.

Advantages are given below:

 Convenience in administration
 Non-invasive and better IVIVC
 Accurate and measured unit dosage form

Limitations of Conventional DDS are given below:

 Poor absorption from target site

 Poor bioavailability
 Fluctuations in plasma drug level
 Repeated dosages
 High dose dumping
 Premature excretion from body

3.2. Advantages and limitations of Controlled DDS:

Controlled DDS with enhance controlled drug release over conventional DDS have more advantages
which are:

 Target specifically
 Long residence of drug
 Improved bioavailability
 Better patient compliance

Controlled DDS despite their advantages over conventional DDS have limitations which are given
below:

 Possible toxicity of the materials being used.

 Dose dumping.
 Invasive procedure to implant.
 Poorer IVIVC3
 Higher manufacturing cost and limited standards.

4. Advancements in biomaterials in CRDDS:

There has been enormous advancement in controlled drug delivery systems in the past two decades.
Nevertheless, there is still scope for advancement to combat the limitations and expand future
possibilities.

3
IVIVC: in vivo in vitro Co-relations

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4.1. CRISPR CAS9 Based Systems:

The emergence of CRISPR-based drug release systems marks a significant advancement in tissue-
specific gene editing. Comprising sgRNA and Cas9 endonuclease, this system directs Cas9 to specific
target sites based on RNA and DNA sequences. Efforts are underway to mitigate off-target effects,
making it applicable for delivering protein drug substances beyond Cas9. [5]

4.2. Microfluidics in Controlled Drug Delivery:

Microfluidics, also known as lab-on-a-chip technology, offers precise drug delivery through controlled
fluid flow and synthetic polypeptides. It facilitates drug release programming by manipulating
polypeptide properties. Additionally, microfluidics finds applications in antibody discovery and cell
delivery, making it a promising field for future research and development in drug delivery systems. [6]

4.3. Molecularly Imprinted Polymers (MIPs):

Molecularly imprinted polymers (MIPs) are cross-linked polymers with specific binding sites for
target molecules. They're developed from five components: template, cross-linker, porogen, monomer,
and initiator. MIPs mimic natural antibody-antigen systems, selectively binding templated molecules
like a lock and key. They show promise in vaccine and drug delivery due to their drug-target
specificity. [7]

Figure 3 Molecular Imprinting polymers synthesis protocol.

4.4. Quantum sensing Drug delivery:

Quantum dots (QDs) serve as a pivotal link between nanotechnology and drug assays. These carbon-
based nanoparticles offer exceptional optical properties, emitting fluorescence upon excitation. With
their superior spectral characteristics, QDs enable real-time tracking of drugs, overcoming limitations
associated with conventional polymer-based carriers. They hold promise as nano-probes and drug
carriers in biomedical applications, facilitating precise drug delivery and RNA transport. [8]

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Biomaterials
Assignment

5. Conclusion:
In conclusion, biomaterials are very important in controlled drug delivery systems to give customized
solutions that will improve the outcome of the therapy while minimizing side effects. The ongoing
innovation of drug delivery technology towards precision medicine is demonstrated by the latest
developments in CRISPR-based systems, microfluidics, molecularly imprinted polymers and quantum
sensing.

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Biomaterials
Assignment

References

[1] F. O.S., O. K.N. and P. P.S., "Advances in biomaterials for drug delivery.," Adv. Mater., 2018.

[2] L. R., "Drug delivery and targeting.," Nature., p. 5–10, 1998..

[3] P. K., "Controlled drug delivery systems: Past forward and future back.," Journal of Controlled
Release., vol. 190, p. 3–8, 2014..

[4] B. D.S., Overby C.T., Sims K.R., and jr., Ackun-Farmmer M.A, Biomaterials Science., Amsterdam, The
Netherlands: Elsevier., 2020.

[5] Deng Y, Zhang X., Shen H., He Q., Wu Z.,, Liao W. and Yuan M., " Application of the Nano-Drug
Delivery System in Treatment of Cardiovascular Diseases.," Frontiers in Bioengineering and
Biotechnology., vol. 7, p. 489, 2020.

[6] Chen R, Sun Z., and Chen D., "Chapter 11—Droplet-based microfluidics for cell encapsulation and
delivery.," in Microfluidics for Pharmaceutical Applications., Amsterdam, The Netherlands., William
Andrew Publishing., 2019, p. 307–335..

[7] Saylan Y., , Akgö nü llü S., , Yavuz H., , Ü nal S and Denizl, "Molecularly imprinted polymer based
sensors for medical applications.," Sensors, vol. 19, p. 1279, 2019.

[8] Preeti S., , Amit B.P. and Subham Jain N., " Application of Quantum Dots in Drug Delivery.," Nanosci.
Nanotechnol. Asia, vol. 1–16., p. 11, 2021.

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