recent advances in micro and nano drug delivery systems

RECENT ADVANCES IN MICRO AND NANO DRUG DELIVERY SYSTEMS

M ROSHINI

13PN02

Targetted Drug Delivery

Nano Drug-delivery

• Nanomedicine uses nanoscale technologies (≤100 nm) for the diagnosis, treatment and/or prevention of diseases

• It includes sustained delivery of Therapeutic Agents, Targeted Delivery Of DrugsReduced Side Effects

Drug delivery carriers

Nanoparticles in drug delivery

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

• Lipid-based nanoparticles – Liposome & Neosome based….

• Polymer-based nanoparticles – Dendrimer,chitosen Micelle based…

• Biological nanoparticles – RGD based…

Metal based nanoparticles

Gold Nanoparticles

• Plasmonic Vesicles of Amphiphilic Gold Nanocrystals: Self-Assembly and External-Stimuli-Triggered Destruction

• Plasmonic vesicular nanostructures assembled from amphiphilic gold nanocrystals with mixed polymer brush coatings.

• Analogous to block copolymers,the disruption of the plasmonic vesicles can be triggered by stimulus mechanisms

• The development of multifunctional vesicles containing stimuli-responsive polymers applications in theragnostic nanomedicine

Self-Assembly and External-Stimuli-Triggered Destruction

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

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

• Gold nps absorb light in the near infra red region becomes hot and can kill the cells in their proximity

Lipid based nps

Liposomes

• Liposomes are small spherical vesicles, composed of lipid bilayers surrounding aqueous inner phase.

• Reservoir (i.e) Bilayers - hydrophobic drugs and inner aqueous phase - hydrophilic drugs

• Liposomes -ocular drug delivery• Encapsulation of idoxuridine into liposomes increased the corneal penetration of

the drug• Variety of biomaterials for ocular drug delivery including

polymeric nanoparticles dendrimers hydrogels

Lipid Nanoparticle Drug Delivery System

• Major problem with IV administration of colloidal particles is interaction with reticulo-endothelial system (RES)

• Any foreign material, biological response to administered nanoparticle, coated by proteins called opsonins, enhance uptake of coated material by RES

• Opsonins on particle surface creates a “molecular signature” recognized by immune cells

• Lipid nanoparticles engineered to evade RES cells by limiting particle sizes to 200 nm or less.

• It is believed that these cells do not recognise low nanometer-sized particles as foreign.

Drug Delivery To BBB

• The BBB is single layer of endothelial cells in inner surfaces of capillaries in the brain

• The endothelial cells fit tightly together and substances cannot pass out of the bloodstream

• The mechanism for transport is endocytosis • Endothelial cells with lipoprotein receptor transports the lipoprotein with

nanoparticle from the blood plasma.

Polymer based nps

Polymeric Nanoparticles On Drug Delivery

• Polymeric nps from natural and synthetic polymers have stability and ease of surface modification

• Polymeric materials-biocompatible and biodegradable • The polysaccharides polymeric materials to prepare nps for drug delivery. • Biodegradable nanoparticles

nanocapsulenanosphere

• The drug molecules are either entrapped inside or adsorbed on the surface.

Chitosan Carrier In Nano Drug Delivery System

• Chitosan (CS) is abundant naturally occurring polysaccharide• Chitosan is made of randomly distributed β-(1-4)-linked D-glucosamine (deacetylated unit)

and N-acetyl-D-glucosamine (acetylated unit) • It is produced by deacetylation of chitin extracted from shells of crabs, shrimps and krill. • Chitosan attracted as

Matrix for controlled release due to its reactive functionalities Easily degradation by enzymes Non-toxic degradation products

• Hydrophobic interactions enhance stability of substituted CS by reducing hydration of matrix ,resisting degradation by gastric enzymes

Polymeric Nanoparticles On Drug Delivery

Chemical Structure Of Chitosan

Biological nanoparticles

TREATING CANCER WITH NANOPARTICLES

• Cancer therapeutics,chemotherapy serious side effects –Devastation of healthy tissueSome cancerous tissue survives after radiation

• Nanoparticles -targeted drug delivery systems  • Nps with UV-sensitive proteins,assemble with drug and cancer cell-

targeting protein fragment when exposed to UV.• Nanoparticle-drug complex that specifically attaches to cancerous cells.  

Reference

• [1] Maeda, H., Wu, J., Sawa, T., Matsumura, Y., and Hori, K. (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J. Controlled Release 65, 271-84.

• [2] Palmer, T. N., Caride, V. J., Caldecourt, M. A., Twickler, J., and Abdullah, V. (1984) The mechanism of liposome accumulation in infarction. Biochim. Biophys. Acta 797, 363-8.

• [3] Jaracz, S., Chen, J., Kuznetsova, L. V., and Ojima, I. (2005) Recent advances I tumortargeting anticancer drug conjugates. Bioorg. Med. Chem. 13, 5043-54.

• [4] Torchilin, V. P. (2004) Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol. Life Sci. 61, 2549-59.

• [5] Gabizon, A., Shmeeda, H., Horowitz, A. T., and Zalipsky, S. (2004) Tumor cell targeting of liposome-entrapped drugs with phospholipid- anchored folic acid-PEG conjugates. AdV. Drug DeliVery ReV.56, 1177-92.

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