Designing a novel in vitro drug-release-testing method for liposomes prepared by pH-gradient method

Abstract

In order to evaluate the drug-release behavior from pH-gradient liposomal formulation, a simple release-testing method without using biological components was newly designed on the basis of inversed ammonia gradient principle. Various factors influencing drug-release (releasing factor) were examined. As a result, releasing factor's concentration, pH, osmolarity in test fluid, and releasing factor's structure were found to be the critical factors to be optimized. Various vincristine-loaded liposomes with different lipid compositions or with different lipid/cholesterol ratio were tested for drug-release behavior and successfully obtained drug-release profiles reflecting differences in the physicochemical properties of individual liposomes. Furthermore, since the comparative release study of vincristine-loaded liposomes and doxorubicin-loaded liposomes could reproduce the phenomena as other researchers recently reported, a possibility was suggested for the proposed method to estimate the physicochemical status of drug inside of liposomes. Proof of concept study concluded, as a whole, that the novel release-testing method would be useful for a formulation study and also useful as a tool for the quality assurance or quality control in the manufacturing of pH-gradient liposomal products.