controlled drug delivery: from macroformulation to nanotechnology purdue university pharmaceutics...
TRANSCRIPT
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Controlled Drug Delivery:
From Macroformulation to Nanotechnology
PURDUEUNIVERSITY
Pharmaceutics &Biomedical EngineeringPurdue Cancer Center Kinam Park
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Modern medicine would not exist without drugs
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Reasons for the high cost of drug development
New Chemical Entities:
1/4~1/3 are unusable due to unfavorable physicochemical &
biochemical properties
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“One word. Just one word: Plastics. There’s a great future in plastics.”
Plastics
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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
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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.
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Macroformulations
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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
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Transdermal Patches with Microneedles
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Nano Drug Delivery Systems
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Drug Nanoparticles
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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
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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
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Targeting
Cellular Uptake
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Tumour Targeting
Ruth Duncan
EPR Effect Antibody Targeting Magnetic field
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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
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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