Controlled Drug Delivery: From Macroformulation to Nanotechnology

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Presentation transcript:

Controlled Drug Delivery: From Macroformulation to Nanotechnology PURDUE UNIVERSITY Pharmaceutics & Biomedical Engineering Purdue Cancer Center Kinam Park

Modern medicine would not exist without drugs

Reasons for the high cost of drug development New Chemical Entities: 1/4~1/3 are unusable due to unfavorable physicochemical & biochemical properties

Plastics “One word. Just one word: Plastics. There’s a great future in plastics.”

EVOLUTION OF DRUG DELIVERY SYSTEMS Patience Compliance & Convenience Enhancement of Products Extension of product life (or patent life) Delivery of Drugs with Unfavorable Properties Synergistic partnership with drug discovery

Patience Compliance & Convenience Enhancement of Products Once-a-day Once-a-week Once-a-month Once-a-year Once-a-decade On-demand Norplant: Made of Silicone rubber 36 mg levonogestrel. 85 ug/day (later 30 ug/day) up to 7 years.

Macroformulations

EVOLUTION OF DRUG DELIVERY SYSTEMS Patience Compliance & Convenience Enhancement of Products Extension of product life (or patent life) Delivery of Drugs with Unfavorable Properties -Poor water solubility -Poor permeability -Poor stability

Transdermal Patches with Microneedles

Nano Drug Delivery Systems

Drug Nanoparticles

Polymeric Nanostructures for Drug Delivery Polymeric drug Polymer-protein conjugate Polyplex: Polymer-DNA complex Polymer-drug conjugate Polymeric micelle Ruth Duncan: The Dawning Era of Polymeric Therapeutics, Nature Reviews 2:347, 2003

Ideal Drug Delivery Systems 1. High drug loading 2. Drug stability 3. Targeting Long circulation, targeting moiety 4. Cellular absorption Mechanisms 5. Escape from endosome

Targeting Cellular Uptake

Tumour Targeting EPR Effect Antibody Targeting Magnetic field Ruth Duncan

Folate mediated polymeric micelles PEG (Mw:3,400) PLGA (Mw:8,000) Folate 104.9  11.5 nm Figure. Confocal microscopic images of KB cells incubated with (A, B) DOX micelles and (C, D) DOX/FOL micelles in the presence and absence of folate in the medium. Ref.: Journal of Controlled Release (2004) 96, 273-283

Nanotechnology in Drug Delivery Fabrication of nanodevices: Biodegradable Polymers, Hydrogels) Targeting: Homing moiety (EPR, Ab, GPS) Cellular Uptake: Biological, Mechanical Removal from the body: Biodegradable nanodevices