No abstract

In this study, to establish the conditions of a drug release assay for PEGylated liposome formulations that relates with the drug stability profile in serum in vivo, the influences of incubation temperature and serum protein in the release buffer were examined using liposomal doxorubicin (DXR). In in vitro drug release assays, a PEGylated liposomal DXR in phosphate buffered saline (PBS) at 37 degrees C showed higher drug release rate than non-PEGylated formulation although PEGylated liposomal DXR had higher stability than an equivalent non-PEGylated formulation following intravenous injection. When bovine serum albumin (BSA) and increased temperature, 50 degrees C, were used to accelerate drug release from the liposomes and to mimic in vivo result, non-PEGylated liposomal DXR showed conversely higher release than a PEGylated formulation. Since high temperature increased BSA adsorption onto liposomes, BSA may cause non-PEGylated liposomes instability more than PEGylated ones, resulting in the reverse of the drug release rate of both liposomes. This finding suggested that the conditions in the drug release assay with PEGylated liposomal DXR may be able to be set by a combination of BSA and providing additional thermal energy.