PT  - JOURNAL ARTICLE
AU  - Parr, Michael J.
AU  - Masin, Dana
AU  - Cullis, Pieter R.
AU  - Bally, Marcel B.
TI  - Accumulation of Liposomal Lipid and Encapsulated Doxorubicin in Murine Lewis Lung Carcinoma: The Lack of Beneficial Effects by Coating Liposomes with Poly(ethylene glycol)
DP  - 1997 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1319--1327
VI  - 280
IP  - 3
4099  - http://jpet.aspetjournals.org/content/280/3/1319.short
4100  - http://jpet.aspetjournals.org/content/280/3/1319.full
SO  - J Pharmacol Exp Ther1997 Mar 01; 280
AB  - The 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 (Te) included area under the doxorubicin plasma (AUCP) and tumor (AUCT) concentration-time curves. Extended time-course studies evaluating lipid and drug levels in plasma and tumors during 7 days after administration indicated that the Te (AUCT/AUCP) was greater for liposomes that did not contain PEG-PE. The AUCP 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 μmol·ml−1·h, 50 μmol·ml−1·h and 78 μmol·ml−1·h, respectively. Maximum drug levels achieved in the tumors were similar for both liposomal doxorubicin formulations, 140 μg (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 μg/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. The American Society for Pharmacology and Experimental Therapeutics