PENTAMIDINE-LOADED POLY(D,L-LACTIDE) NANOPARTICLES - ADSORPTION AND DRUG-RELEASE

This work describes the loading capacity of poly(D,L-lactide) nanopart icles, the factors influencing pentamidine release, and the cytotoxici ty of nanoparticles. The nanoprecipitation method was used to prepare pentamidine-loaded poly(D,L-lactide) nanoparticles. Various concentrat ions of pentamidine base and polymer were tested. The influence of the dilution, temperature, and ionic strength was evaluated. The cytotoxi city on J 774 cells of unloaded nanoparticles, pentamidine-loaded nano particles, and pentamidine isethionate were tested. The percentage of binding decreased significantly with drug load. A nonlinear increase i n drug uptake per unit mass of polymer with the equilibrium pentamidin e concentration was found. A Langmuir-type sorption was suggested (r = 0.998). 390 mu g/ml was found to be the highest level of drug incorpo ration. The increase of polymer concentration did not improve the pent amidine fixation yield. The increase in temperature or buffer molarity induced a significant release of pentamidine. The increase in dilutio n also induced an increase in release of pentamidine. The cytotoxicity of pentamidine-loaded nanoparticles and unloaded nanoparticles was su perimposable. After 24 h of incubation, pentamidine-loaded nanoparticl es presented an IC50 value significantly lower than that of free drug( 0.39 vs. 6.5 g/ml). (C) 1998 Wiley-Liss, Inc.