Sustained interferon-gamma delivery from a photocrosslinked biodegradable elastomer.
The application of protein therapeutics for long-term, localized delivery has been hindered by a lack of a delivery device that releases active protein at a concentration within their therapeutic window. A protein delivery system that uses an osmotic pressure delivery mechanism and a photocrosslinked biodegradable elastomer has been designed in an attempt to overcome this limitation. The elastomer is prepared through the UV initiated crosslinking of end terminal acrylated star-poly(epsilon-caprolactone-co-D,L-lactide). Interferon-gamma (IFN-gamma) was released from the optimum formulation at a constant rate of 23 ng/day over 21 days. A cell-based assay showed that over 83% of released IFN-gamma was bioactive. Furthermore, it was demonstrated that bovine serum albumin co-lyophilized with IFN-gamma was released at the same rate as IFN-gamma. This delivery formulation may be clinically useful for sustained, local protein drug delivery applications.
Gu
Frank
F
Department of Chemical Engineering, Queen's University, Kingston, ON, Canada K7L 3N6.
Younes
Husam M
HM
El-Kadi
Ayman O S
AO
Neufeld
Ronald J
RJ
Amsden
Brian G
BG
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000528:radiation effects; D016503:Drug Delivery Systems / Q000379:methods*; D020724:Elastomers / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects; D051379:Mice; D014466:Ultraviolet Rays
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D020724:Elastomers; D007371:Interferon-gamma