Coating of indomethacin-loaded embolic microspheres for a successful embolization therapy

Abstract

Indomethacin-loaded dietheylaminoethyl trisacryl Õ microspheres (DEAE-MS), originally designed for therapeutic embolization, were encapsulated using two methods: coacervation and solvent evaporation/extraction. This encapsulation was achieved using a biocompatible polymer, the PLGA 50 : 50, and aimed to control the release of the anti-inflammatory non-steroidal drug (AINSD) in the occluded vessel. PLGA degradation study showed that it had an erosion half-life of $35 days. Scanning electron microscopy (SEM) photographs showed that microcapsules (MC) prepared by coacervation had a wrinkled surface while those prepared using solvent-removal process showed non-porous, smooth surface, those of originally DEAE-MS showed a macroporous, rough surface. The mean diameters were 61 mm for naked DEAE-MS vs. 71 mm and 65 mm for MC prepared by coacervation and solvent evaporation/extraction method, respectively. In vitro release study of indomethacin adsorbed onto MS indicated that drug release from MC was controlled by a diffusion process. Indomethacin diffusivity from MC was much lower than its free diffusivity from MS (mean 14.5 and 10.5 times lower for formulations prepared by coacervation and solvent evaporation/extraction method, respectively). This indicates that efficient indomethacin concentrations could be maintained over much longer time-periods in the embolized region, which is assumed to be beneficial in inhibiting normally occurring inflammatory reaction and the subsequent revascularization; responsible for treatment failure when definitive occlusion is required.