Transcript Oral Drug Delivery - Purdue University

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
Polymer-drug conjugate
Polyplex: Polymer-DNA complex
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
Ruth Duncan
Antibody Targeting
Magnetic field
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