Mechanistic model and analysis of doxorubicin release from liposomal formulations

摘要: Reliable and predictive models of drug release kinetics in vitro vivo are still lacking for liposomal formulations. Developing robust, requires systematic, quantitative characterization these complex delivery systems with respect to the physicochemical properties governing driving force release. These must also incorporate changes due dissolution media methods employed monitor This paper demonstrates successful development application a mathematical mechanistic model capable predicting doxorubicin (DXR) from formulations resembling FDA-approved nanoformulation DOXIL® using dynamic dialysis. The accounts DXR equilibria (e.g. self-association, precipitation, ionization), change intravesicular pH ammonia release, dialysis membrane transport DXR. was tested Box-Behnken experimental design which conditions including extravesicular pH, concentration medium, dilution formulation (i.e. suspension concentration) were varied. Mechanistic predictions agreed observed up 19h. similar computer fit data an empirical often analyzing generated this type design. Unlike model, able provide reasonable outside space. results illustrate usefulness modeling predict its potential future - correlations nanoformulations.