NANOAPRTICLES IN DRUG TARGETING

A REVIEW
By
Shrey Bhatt
T.Y.B.Pharm
S.C.O.P

GUIDED BY
Mrs.Vaishali Gambhire

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 INTRODUCTION

NANOPARTICLES
  

 Nanoparticles are in solid state and are either in amorphous or crystalline state.

 They are able to adsorb or encapsulate a drug thus protecting it against chemical and enzymatic

degradation. Their size ranges from 1-100nm.

 Nanocapsules:They are vesicular systems in which drug is confined to a cavity surrounded by a

unique polymer membrane.

 Nanospheres:They are matrix systems in which a drug is uniformly dispersed.

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 PRIME FOCUS

 In this review we focus on the role of nanotechnology in drug targeting and

delivery.

 There is a need to develop suitable drug delivery systems that distribute the
therapeutically active drug molecule only to the site of action, without
affecting healthy organs and tissues

 Thus it results in lowering doses required for efficacy as well as increasing the
therapeutic indices and safety profiles of new therapeutics.

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 APPLICATIONS OF NANOPARTICLES

 The transition from micro- to nanoarrays will enable more accurate and
precise drug targeting.

 It will lead to in­troduction of personalised therapies spe­cifically tailored to the

genetic profile of the patient.

 Nanoparticles are used in advanced drug delivery systems to target diseased

cells and increase drug uptake and efficacy.

 They also minmize side effects, and as contrast agents for medical imaging.

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 Gold nanoparticles functionalised with antibodies to bind them to cancer cells create
intense image contrast due to their scattering properties.

 Laser light absorbed by these particles is converted into heat that selectively de­stroys the
cancer cells without harming the surrounding healthy tissue.

Fig. 1 : Image of cancer cell decorated with gold nanorods bound to anti-EFGR.

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 NANOPARTICULATE SYSTEMS FOR DRUG
TARGETING

1.Drug Nanoparticles:
 Dispersion of drug particles in the nanosize range in an aqueous environment is an attractive

approach for the delivery of water insoluble drugs.

2. Solid Nanoparticles:
(a) Polymer Nanoparticles
 These nanoparticles are made from copolymers to increase circulation half-life and reduce the MPS

[Mononuclear Phagocytic System]uptake.

Fig 2 : Polymer Nanoparticles

 

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(b) Lipid Based Nanoparticles:
 Solid lipid nanoparticles are nanosclae carriers that have advantages like use of physiological lipids.

Fig 3 : Lipid Nanoparticles

(c) Ceramic Based Nanoparticles:

 Nanoparticles made up of ceramic materials such as silica alumina and titania have several
advantages over polymeric particles.

 Their preparations are simple similar to the well-known sol-gel process and require ambient
temperature conditions.

 The particles can be prepared to the desirable size shape porosity and are extremely inert.
 

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 Fig 3:Ceramic Nanoparticles

(d) Albumin Based Nanoparticles:

 Albumin is major protein in serum.
 Albumin surface possess several amino and carboxyl groups, which are available for covalent
modification and drug or protein attachment .

Fig 4: Albumin Nanoparticles

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(e) Nanogels :

 Nanogels composed of flexible hydrophilic polymers in the nanosize scale can be

made in the absence of drug.
 Upon swelling in water drug can be loaded spontaneously into the nanogel
resulting in reduction of the solvent volume.
 Leads to gel collapse and formation of dense nanoparticles.

Fig 5 : Nanogels

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 DRUG TARGETING

Drug targeting can be further divided into two main types and they are:

1.Passive Targeting:
Passive targeting occurs due to extravasations of the nanoparticles at the diseased

site where the microvasular is leaky.

2.Active Targeting :
Localized diseases like cancer and inflammation have leaky vasculature and over

express some epitopes that are used as targets.

Therefore nanomedicines can also be actively targeted to these sites

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 VARIOUS APPROACHES TO DRUG TARGETING

1.Tumor targeted delivery of encapsulated dextran–doxorubicin conjugate

using chitosan nanoparticles as carriers :

 Doxorubicin used in cancer therapy produces undesirable side effects such as cardio
toxicity.

 To minimize these, attempts have been made to couple the drug with dextran and then to
encapsulate this drug conjugate in hydrogel nanoparticles.

 By encapsulation of the drug conjugate in biodegradable,biocompatible long circulating

hydrogel nanoparticles, it improved the therapeutic efficacy of the conjugate.

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 2. Targeted nanoparticles for drug delivery through the
blood–brain barrier for Alzheimer’s disease

 Alzheimer’s disease (AD) is the most common cause of dementia among

the elderly, affecting 5% of Americans over age 65, and 20% over age 80.

 Unfortunately, targeted drug delivery to the central nervous system,for the

therapeutic advancement of neurodegenerative disorders such as Alzheimer’s is
complicated by restrictive mechanisms imposed at the blood–brain barrier.

 The study suggests that biodegradable polymeric nanoparticles with appropriate

surface modifications can deliver drugs of interest beyond the BBB for
diagnostic and therapeutic applications in neurological disorders, such as AD.

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 Vitamin B12-Nanoparticle Conjugates as Constructs for
Targeted Tumor Delivery and for Oral Drug Delivery

 Vitamin B12 is used for targeted delivery of drugs to disease sites and for oral drug
delivery of drugs that otherwise have poor oral bioavailability.

 Cobalamin-coated nanoparticles can provide a substantial lowering of blood

glucose levels in an animal model of diabetes , compared to unformulated insulin
given orally.

 Cobalamin- targeted polymer-linked daunorubicin reduces tumor volume after

intravenous administration in an animal model, providing superior efficacy when
compared to polymer-daunorubicin without the targeting group.

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Targeted Nanoparticle delivery systems and siRNA design to
create effective therapeutics

 The siRNA delivery system has been designed for intravenous injection.

 Upon delivery to the target cell, the targeting ligand binds to membrane receptors on
the cell surface and the RNA-containing nanoparticle is taken into the cell by
endocytosis.

 Calando have demonstrated successful delivery of functional siRNA therapeutics to

tumor cells and to hepatocytes by systemic administration and confirmed sequence
specific gene inhibition.

 Calando’s technology can be used with various targeting ligands. In addition to

targeting tumors, the targeting of liver has also been accomplished.

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Histological studies validate Rexin-G as targeted gene therapy
for cancer

 Rexin-G is "the world's first tumour-targeted genetic medicine for cancer therapy.”

 Rexin-G is currently in Phase I/II clinical trials in the US for metastatic or locally
advanced pancreatic cancer.

 Rexin-G is approved under an expanded access programme in the Philippines for

use as a first-line and adjuvant therapy for pancreatic and breast cancer.

 Also as a second-line therapy for all other solid tumours refractory to standard
chemotherapy.

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 The Nanoparticle Drug Delivery Market

 Total market for nanotechnology-enabled drug delivery will rise to $26 billion by
2012 from its current size of $3.39 billion, representing a compound annual growth
rate of 37%.

 But this is just the beginning; the market could steeply rise after 2012, reaching
potentially $220 billion by 2015 for these nano-enabled compounds.

 There are over 60 different companies, including 38 drug formulation companies

and 23 drug delivery companies analyzing where they are in their product pipeline.

 There are 58 case studies of nanoparticle drug delivery platforms and technologies

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 FUTURE BARRIERS AND CHALLENGES

 
 Big Pharmaceutical Companies Reluctant To Invest In Untried Technologies
 
 Lack Of Regulatory Case Law
 
 Long Admission Procedures Including For Example Several Clinical Trials.
 
 Need For Rapid Screening Methods.
 
 Scalability of nanoparticle production.
 
 An urgent Need For Analytical Methods
 
 The Potential Toxicity Of Engineered Nanoparticles Is Unsolved.

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VARIOUS NANOPHARMACEUTICALS AND THEIR CASE
STUDIES
CANCER THERAPY:
 
 Case Study -- Nanocarrier’s Micellar Nanoparticles And Key Delivery Systems

 Case Study -- Abraxis BioScience’s Nanoparticle Albumin Bound (nabTM)

Technology Platform

VACCINES:
 Case Study -- Biosante Pharmaceuticals’ Calcium Phosphate Nanoparticles (CAP)-

based Technology
 Case Study -- NanoMed's Nanotemplate Engineering Technology

ANTIBODY:
 Case Study -- Ablynx’s Nanobody® Platform

 Case Study - NanoViricides’ Targeted Anti-Viral Therapeutics Platform

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 NANOPARTICLE DRUG DELIVERY SYSTEM BY TECHNOLOGY

NANOPARTICULATE ENCAPSULATION:
 Case Study -- Aquanova’s Nanoparticulate Encapsulation Technology

 Case Study -- Bio Delivery Sciences International’s Bioral® Encochleation Drug

Delivery Technology

NANOTUBE TECHNOLOGIES:
 Case Study -- Biophan Technologies’ Halloysite Nanotube Technologies

 Case Study -- NanoCyte’s Nanotube Technology-based Drug Delivery System

 
NANOSHELL TECHNOLOGY:
 Case Study -- Nanospectra Biosciences’ AuroLase™ Cancer Therapy

NANOSOME TECHNOLOGY:
 Case Study -- Molecular Therapeutics’ Nanosome Platform

 
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 NanoDrug Patenting

 Nanotechnology is still in its infancy and filing nanotech patents has become a
grabbing excercise.

 There have been few nanotech patent disputes because companies are yet to
commercialize their nanotechnology discoveries.

 This will expose us to strategic risks as other sectors invest in this technology.

 If this trend continues, nanotech will play out in pharmaceuticals just as

biotechnology did.

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Nanotech Meets the FDA: A Success Story about the First Nanoparticulate Drugs Approved by the FDA
 

 The first three nanodrugs Emend® ,Tricor®, Rapamune®, were

 approved by the FDA.
 
 As of now, 130 nanotech-based drugs and delivery systems and 125
devices or diagnostic tests are in preclinical, clinical or commercial
development.”

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 CONCLUSION

 Adoption of Nanotechnology by Big Therapeutic and Diagnostic Companies

Gives an Impetus to Nanomedicine.

 The emphasis on biophysical attributes of the drug targeting platforms as well as

the biological aspects that enable targeting of these platforms to injured and
diseased tissues and cells are very important.

 Pharmaceuticals, biopharmaceuticals, and drug delivery companies are

increasingly adopting nanotechnology-based applications.

 The potential of emerging nanomedicine technologies to provide site-specific

therapeutic action with a better side effects profile is a strong point in favor of this
pioneering form of medicine.

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 REFERENCES
[1] URL :
http: // www.nanofroum.org/nf06

[2] S. Mitraa, U. Gaura, P.C. Ghosha, A.N. Maitrab , Tumour targeted delivery of
encapsulated dextran–doxorubicin conjugate using chitosan nanoparticles as carrier
Journal of Controlled Release 74 (2001) 317–323

[3] Celeste Roney a, Padmakar Kulkarni Targeted nanoparticles for drug delivery through
the blood–brain barrier for Alzheimer’s disease Journal of Controlled Release 108
(2005) 193–214

[4] URL:
http://www.biomedicine.org/medicine technology

[5] URL:
http://www.calandopharma.com/rnai.html

[6] URL:
http://www.inpharmatechnologist.com/news-by-month

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THANK YOU

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