PLGA/PVA hydrogel composites for long-term inflammation control following s.c. implantation.
Dexamethasone loaded PLGA microsphere/PVA hydrogel composites were investigated as an outer drug-eluting coating for implantable devices to provide protection against the foreign body response. Two populations of microspheres were prepared: 25 kDa PLGA microspheres which had a typical triphasic release profile extending over 30-33 days; and 75 kDa PLGA microspheres which showed minimal release for the first 25 days and then increased to release over 80-85 days. Incorporation of the microspheres in the composites only slightly altered the release profile. Composites containing 25 kDa microspheres released dexamethasone over 30-35 days while composites containing combinations of 25 and 75 kDa microspheres in equal amounts released over 90-95 days. Pharmacodynamic studies showed that composites containing only 25 kDa microspheres provided protection against the inflammatory response for 1 month, however, a delayed tissue reaction developed after exhaustion of dexamethasone. This demonstrated that sustained release of the anti-inflammatory agent is required over the entire implant lifetime to control inflammation and prevent fibrosis. Composites fabricated using combinations of 25 kDa and 75 kDa microspheres controlled the tissue reaction for 90 days. This strategy of combining different microsphere populations in the same composite coating can be used to tune the release profiles for the desired extent and duration of release. Such composites offer an innovative solution to control the foreign body response at the tissue-device interface.
School of Pharmacy, University of Connecticut, 69 North Eagleville Rd, Unit 3092, Storrs, CT 06269, USA. upkar.bhardwaj@uconn.edu
Upkar
U
Bhardwaj
Radhakrishana
R
Sura
Fotios
F
Papadimitrakopoulos
Diane J
DJ
Burgess
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D004343:Drug Implants; D020100:Hydrogels / Q000008:administration & dosage* / Q000009:adverse effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D019344:Lactic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008863:Microspheres; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D040521:Subcutaneous Tissue / Q000187:drug effects / Q000473:pathology*; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004343:Drug Implants; D020100:Hydrogels; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol