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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