EFFECTS OF DIFFERENT PHOSPHOLIPIDS ON THE STABILITIES OF DOXORUBICIN LIPOSOMES IN VITRO AND IN VIVO

AIM To study the effects of egg phosphatidylcholine (EPC) and hydrogenated egg phosphatidylcholine (HEPC) on the leakage of doxorubicin liposome in vitro and the resident time in blood. METHODS By the means of dialysis, the leakage of EPC (EPC-NL) and HEPC normal liposomes (HEPC-NL) in fetal cattle serum (FCS) was determined at 37℃ and in phosphate buffer solution (PBS) at 37℃, 20℃ and 4℃. Furthermore, the pharmacokinetics of EPC and HEPC sterically stabilized liposomes (EPC SSL and HEPC-SSL) were studied by HPLC. RESULTS The leakage of doxorubicin from HEPC-NL is slower than that of EPC-NL in FCS at 37℃. But in PBS at all of three different temperatures, the results are completely reversed, i.e., the leakage of EPC-NL is slower than that of HEPC-NL. Further studies on pharmacokinetics showed that the mean residence time of HEPC-SSL in blood is 23.3 h, while that of EPC-SSL is 12.0 h, and the area under the curve (AUC) of concentration of HEPC-SSL is larger than that of EPC-SSL. CONCLUSION HEPC-SSL is a better carrier in delivering the drugs to the extravascular sites than EPC-SSL.