Controlled release of vancomycin from biodegradable microcapsules

Poly D,L-lactic acid (PLA) and its copolymers with glycolide PLGA 90:10 and 70:30 were polymerized under various conditions to yield polymers in the m olecular weight range 12 000-40 000 daltons, as determined by gel permeatio n chromatography. Vancomycin hydrochloride was the hydrophilic drug of choi ce for the treatment of methicillin resistant Staphyloccoccal infections. I t was microencapsulated in the synthesized polymers using water-oil-water ( w/o/w) double emulsion and solvent evaporation. The influence of microcapsu le preparation medium on product properties was investigated. An increase i n polymer-to-drug ratio from 1:1 to 3:1 caused an increase in the encapsula tion efficiency (i.e. from 44-97% with PLGA). An increase in the emulsifier (PVA) molecular weight from 14-72 kD caused an increase in encapsulation e fficiency and microcapsule size. The in vitro release of vancomycin from mi crocapsules in phosphate buffer saline (pH 7.4) was found to be dependent o n molecular weight and copolymer type. The kinetic behaviour was controlled by both diffusion and degradation. Sterilization with Co-60 (2.5 Mrad) als o affected the degradation rate and release profiles. Degradation of microc apsules could be seen by scanning electron microscopy, by the increase in t he release rate from PLA and by the decrease in the Tg values of microcapsu les. In vitro bactericidal effects of the microcapsule formulations on S. a ureus were determined with a special diffusion cell after the preparations had been sterilized, and were found to have bactericidal effects lasting fo r 4 days.