Characterization and Pharmacokinetic Evaluation of Oxaliplatin Long‐Circulating Liposomes

The clinical efficacy of Oxaliplatin (L‐OHP) is potentially limited by dose‐dependent neurotoxicity and high partitioning to erythrocytes in vivo. Long‐circulating liposomes could improve the pharmacokinetic profile of L‐OHP and thus enhance its therapeutic efficacy and reduce its toxicity. The purpose of this study was to prepare L‐OHP long‐circulating liposomes (L‐OHP PEG lip) by reverse‐phase evaporation method (REV) and investigate their pharmacokinetic behavior based on total platinum in rat plasma using atomic absorption spectrometry (AAS). A simple and a sensitive AAS method was developed and validated to determine the total platinum originated from L‐OHP liposomes in plasma. Furthermore, long‐circulating liposomes were fully characterized in vitro and showed great stability when stored at 4°C for one month. The results showed that the total platinum in plasma of L‐OHP long‐circulating liposomes displayed a biexponential pharmacokinetic profile with five folds higher bioavailability and longer distribution half‐life compared to L‐OHP solution. Thus, long‐circulating liposomes prolonged L‐OHP circulation time and may present a potential candidate for its tumor delivery. Conclusively, the developed AAS method could serve as a reference to investigate the pharmacokinetic behavior of total platinum in biological matrices for other L‐OHP delivery systems.