November 8, 2011

Sumit Kumar Pramanik

Indian Institute of Chemical BiologyJadavpur

Nanotechnology Based Drug Delivery

(I) Introduction –

a) what is nanotechnolgy? b) So far its major application

(II)Nanotechnology in drug delivery – a) Why nanoparticle is used? b) Different examples

(c) Conclusion

(I) Introduction: What is Nano-scale ?

1.27 × 107 m 0.22 m 0.7 × 10-9 m

Fullerenes C60

12,756 Km 22 cm 0.7 nm

10 millions times smaller

1 billion times smaller

Applications of Nanotechnology in day to day life….

Information Technology Energy

Medicine

Consumer Goods

•Smaller, faster, more energy efficient and powerful computing and other IT-based systems

•More efficient and cost effective technologies for energy production− Solar cells− Fuel cells− Batteries− Bio fuels

•Foods and beverages−Advanced packaging materials, sensors, and lab-on-chips for food quality testing

•Appliances and textiles−Stain proof, water proof and wrinkle free textiles

•Cancer treatment•Bone treatment•Drug delivery•Drug development•Medical tools•Diagnostic tests• Imaging

Applications of Nano-biotechnology in therapeutics:

•Medical Diagnostic tools and Sensors•Drug Delivery•Pharmacocatalysis•Medical Imaging•Filters

Challenges to make the drug more effective via Nanotechnology:

Prevention of drug from biological degradation

Effective TargetingPatient ComplianceCost effectivenessProduct life extension

Nanotechnology in Cancer therapy:

Diagnosis using Quantum DotsTumor Targeted DeliveryImagingCancer Gene Therapy etc….

Nanoparticles for Drug Delivery

Metal-based nanoparticles – Au, Ag, Cd-Se, Zn-S etc

Lipid-based nanoparticles – Liposome & Neosome based….

Polymer-based nanoparticles – Dendrimer, Micelle

Biological nanoparticles – Bovine-albumin serum based…

The following different types of np-based drug-delivery systems will be discussed elaborately ….

Thermal ablation of cancer cells by ‘Silica-gold’ nano shells

Thermal ablation of cancer cells assisted by nanoshells coated with metallic layer and by applying an external energy source to kill them…..

Gold Nanoparticles

surrounding appropriate dielectric materials can absorb light in the near infra red region which becomes hot and can kill the cells in their proximity. This technique has now been used for the treatment of cancer.

Gastrin Releasing Protein (GRP) Receptor Specific Gold Nano-rods

General structure of GNR-BBN conjugates.

GNR-BBN conjugates have very high binding affinity toward GRP receptors in cancer cells and can easily enter into the cancer cell.

The selective delivery of GNRs to tumoral region can be achieved by attaching a target-specific protein (BBN).

Bombesin (BBN)Gold nanorod (GNR)

Quantum Dot Based Drug Delivery System to Target Cancer

Quantum Dots conjugated to peptide/antibodies specific against the cancer marker on the surface of the target cancer cells would be made to release the drug only when hit with laser light. This would allow control of the cells that will receive the toxin, thus minimizing side effects.

Quantum Dots:Quantum dots are tiny particles, or “nanoparticles”, of a semiconductor material, traditionally chalcogenides (selenides or sulfides) of metals like cadmium or zinc (CdSe or ZnS, for example), which range from 2 to 10 nanometers in diameter (about the width of 50 atoms). 

Brain-The ultimate target for drug delivery

The mechanism for transport is due to endocytosis via the low density lipoprotein receptor of endothelial cells after absorption of lipoproteins from blood plasma to the nanoparticles.

The BBB is formed by the single layer of endothelial cells that line the inner surfaces of capillaries in the brain. In the brain, the endothelial cells fit tightly together and substances cannot pass out of the bloodstream.

Lipid-based Drug Delivery

Niosome based drug delivery:

Polymer based nano-technology:Micelle

Micelle is an aggregate of amphiphilic molecules in water, with the nonpolar portions in the interior and the polar portions at the exterior surface, exposed to water….

Dendrimers

These branched macromolecules are constructed around a simple core unit.

Dendrimers have a high degree of molecular uniformity, narrow molecular weight distribution, specific size and shape characteristics, and a highly- functionalized terminal surface.

Polymeric Nano-particles

Polymeric Nano-particles

In recent years, biodegradable polymeric nanoparticles have attracted considerable attention as potential drug delivery devices in view of their applications in drug targeting to particular organs/tissues, as carriers of DNA in gene therapy, and in their ability to deliver proteins, peptides and genes.

Carbon 60

Carbon 60

C60 are spherical molecules about 1nm in diameter, comprising 60 carbon atoms arranged as 20 hexagons and 12 pentagons: the configuration of a football.

It has nanopharmaceuticals application as antimicrobial agent in view of its potency for induction of reactive oxygen species after photo excitation.

On the other hand with development of various chemical substitutes for C60, it is possible to develop functionalized C60 with better drug targeting properties

Carbon Nanotube

Biological nano-particles from bovine-serum albumin for drug delivery

The disadvantages in use of liposome which has low encapsulation efficiency, rapid leakage of water-soluble drug in presence of blood component and poor storagestability.

The benefits of protein nanoparticles are: nontoxicity, stability for long duration,non-antigen also posse biodegradability.

Drug Delivery Carriers:

Significant achievements of nano-technology so far:

Development of one dose a day ciprofloxacin using nanotechnology

Tumor targeted taxol delivery using nanoparticlesImproved ophthalmic delivery formulation using smart

hydrogel nanoparticlesOral insulin formulation using nanoparticles carriers.Liposomal based Doxorubicin B formulation

Conclusion

• It involves low cost research compared that for discovery of new chemical entity.

• Minimizing the drug usage would significantly reduce the effective cost of drug which would give financial relief to the patients.

• Novel means of delivery particularly using nano-carriers, can allow branded drugs to be rescued from abyss of generic competition.

Acknowledgement

To my Supervisor Dr. Biswadip Banerji, My labmates,

Faculty of chemistry Departments, My friends of IICB

Thanks