Cholesterol and lecithin implants for sustained release of antigen: release and erosion in vitro, and antibody response in mice

Abstract

Implantable matrix systems (pellets) were prepared from cholesterol (C), and from C and lecithin (PC), with bovine serum albumin (BSA) as a model antigen. The release profile of BSA from these pellets and their erosion behaviour in borate buffer (pH 7.4) were studied in vitro under different hydrodynamic conditions. The effect of different methods used to mix C and PC on release profile and erosion behaviour was also investigated; pellets were made from physically mixed and coprecipitated C and PC. Ethanol, ethanol-chloroform (1:1, v/v) and chloroform were used as coprecipitating solvents. BSA was released by diffusion from all pellets and increasing the concentration of PC enhanced the rate of release. The erosion rate of C and PC depended on the C-PC composition of pellets. Both the release of BSA and erosion of pellets were positively influenced by hydrodynamic activities. At a C-PC ratio of 1:2 w/w (approx. 1 : 1 molar), a paracrystalline hydrated phase (gel) was formed which was not a diffusional barrier for the release of BSA. Chloroform used as a coprecipitating solvent reduced the rate of release of BSA significantly at C-PC ratios of 2:1 and 1:1 (w/w). Erosion of pellets occurred when implanted subcutaneously in mice for 40 days. Implantation of mice with the different formulations containing BSA induced significant ( P ≦ 0.0001) antibodies to BSA in all groups at 40 days, but the levels did not differ significantly between groups (P ≧ 0.088).