• M J Parr, D Masin, P R Cullis, and M B Bally.
• Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada.
• J. Pharmacol. Exp. Ther. 1997 Mar 1; 280 (3): 1319-27.

AbstractThe efficiency of drug accumulation in tumors was measured after intravenous administration of doxorubicin encapsulated in distearoyl phosphatidylcholine/cholesterol liposomes prepared in the presence or absence of 5 mol % polyethylene glycol-modified phosphatidylethanolamine (PEG-PE). These liposomal formulations of doxorubicin were administered at the maximum tolerated dose in female BDF-1 mice bearing subcutaneously established Lewis Lung carcinoma. The parameters used to determine tumor targeting efficiency (T(e)) included area under the doxorubicin plasma (AUC(P)) and tumor (AUC(T)) concentration-time curves. Extended time-course studies evaluating lipid and drug levels in plasma and tumors during 7 days after administration indicated that the T(e) (AUC(T)/AUC(P)) was greater for liposomes that did not contain PEG-PE. The AUC(P) after administration of free doxorubicin, doxorubicin encapsulated in distearoyl phosphatidylcholine/cholesterol liposomes and doxorubicin encapsulated in distearoyl phosphatidylcholine/cholesterol/PEG-PE-stabilized liposomes were 0.087 micromol x ml(-1) x h, 50 micromol x ml(-1) x h and 78 micromol x ml(-1) x h, respectively. Maximum drug levels achieved in the tumors were similar for both liposomal doxorubicin formulations, 140 microg (250 nmol)/g tumor; however, this level was achieved faster when the liposomes did not contain PEG-PE. Maximum levels measured after administration of free drug were less than 5 microg/g tumor, and these were achieved within 15 min. The results suggest that some of the benefits associated with the use of PEG-modified liposomes, such as increased blood levels and enhanced circulation lifetime, may be of little advantage in terms of maximizing liposomal drug accumulation in sites of tumor growth.

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