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

2. Modern medicine would not exist without drugs

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

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

6. 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

7. 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.

8. Macroformulations

9. 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

12. Transdermal Patches with Microneedles

13. Nano Drug Delivery Systems

14. Drug Nanoparticles

15. 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

16. 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

17. Targeting
Cellular Uptake

18. Tumour Targeting EPR Effect Antibody Targeting Magnetic field
Ruth Duncan

19. 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,

20. 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