Bioabsorbable Microspheres for Local Drug Release in the Articulus

Abstract

Bioabsorbable microspheres incorporating an anti-inflammatory drug, dexamethasone, were prepared from poly(d,l-lactic acid) (PDLLA) using different molecular weights (Mws) by a solvent evaporation method using oil-in-oil emulsion. Two types of PDLLA microspheres with diameter ranges of 40-60 and 90-110 μm were obtained by changing the stirring speed. The microspheres prepared from the higher Mw PDLLA degraded more slowly in phosphate-buffered saline solution (PBS, pH 7.4) than those from the lower Mw PDLLA. The release of incorporated drug into PBS from each PDLLA microspheres was assessed by high performance liquid chromatography. Faster drug release was observed from smaller microspheres. The microspheres prepared from PDLLA with lower Mws released faster the drug than those from PDLLA with higher Mws. Drug concentration in the serum was high immediately after intra-articular injection of dexamethasone in the free form and thereafter decreased with time. In contrast, no drug was detected in the serum of rabbits over the time range studied when injected with dexamethasone-incorporated PDLLA microspheres. This finding indicates that drug release from the microspheres is localized in the articulus.