Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devices.
The purpose of this research was to develop polylactic-co-glycolic acid (PLGA) microspheres for continuous delivery of dexamethasone for over a 1-month period, in an effort to suppress the acute and chronic inflammatory reactions to implants such as biosensors, which interfere with their functionality. The microspheres were prepared using an oil-in-water emulsion technique. The oil phase was composed of 9:1 dichloromethane to methanol with dissolved PLGA and dexamethasone. Some microspheres were predegraded for 1 or 2 weeks. Ten percent of polyethylene glycol was added to the oil phase in alternative formulations to delay drug release. The in vitro release studies were performed in a constant temperature (37 C) warm room, in phosphate-buffered saline at sink conditions. Drug loading and release rates were determined by HPLC-UV analysis. The standard microsphere systems did not provide the desired release profile since, following an initial burst release, a delay of 2 weeks occurred prior to continuous drug release. Predegraded microspheres started to release dexamethasone immediately but the rate of release decreased after only 2 weeks. A mixed standard and predegraded microsphere system was used to avoid this delay and to provide continuous release of dexamethasone for 1 month.
Hickey
T
T
Center for Biomaterials, University of Connecticut Health Center, Farmington 06030-1615, USA.
Kreutzer
D
D
Burgess
D J
DJ
Moussy
F
F
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology*; D016503:Drug Delivery Systems; D019344:Lactic Acid / Q000494:pharmacology*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000494:pharmacology*; D013997:Time Factors; D014466:Ultraviolet Rays
D000893:Anti-Inflammatory Agents; D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone