Controlled Drug Delivery:

From Macroformulation to Nanotechnology

PURDUEUNIVERSITY

Pharmaceutics &Biomedical EngineeringPurdue 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

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

Plastics

EVOLUTION OF DRUG DELIVERY SYSTEMS

Patience Compliance & ConvenienceEnhancement of Products

Extension of product life (or patent life)

Delivery of Drugs with Unfavorable Properties

Synergistic partnership with drug discovery

Patience Compliance & ConvenienceEnhancement of Products

Once-a-dayOnce-a-weekOnce-a-monthOnce-a-yearOnce-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 & ConvenienceEnhancement 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 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

Polymeric Nanostructures for Drug Delivery

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

Ruth Duncan

EPR Effect Antibody Targeting Magnetic field

Folate mediated polymeric micelles

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.

Folate

PEG(Mw:3,400)

PLGA(Mw:8,000)

104.9 11.5 nm

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