Abstract
To assess the biocompatibility of controlled release microspheres prepared from different polymeric biomaterials in various size ranges in rabbit synovial joints and based on these data, design and evaluate the efficacy of an intra-articular, paclitaxel-loaded microspheres formulation in rabbit models of arthritis. Paclitaxel-loaded microspheres of poly(lactide-co-glycolide) (PLGA), poly(L-lactic acid) (PLA) and poly(caprolactone) (PCL) were prepared in different size ranges and inflammatory responses monitored following injection into healthy rabbit joints. The efficacy of 20% paclitaxel-loaded PLA microspheres (35-105 microm size range) injected intra-articularly into antigen and carrageenan induced rabbit models of arthritis was monitored. Polymeric microspheres in the 35-105 microm size range were biocompatible whereas smaller microspheres (1-20 microm) produced an inflammatory response. Efficacy studies showed that injection of 20% paclitaxel-loaded PLA microspheres significantly reduced all measures of inflammation in the antigen arthritis rabbit model. Paclitaxel-loaded PLA microspheres in the 35-105 microm size range, released paclitaxel in a controlled manner over several weeks, and may be a potential formulation for the intra-articular treatment of inflammation in arthritic conditions.
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