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Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 [F. Y., M. L., D. A. B., R. K. J.], and Cancer Research Institute and Department of Pharmacology, University of California, San Francisco, California 94143 [S. K. H., D. P.]
Microvascular permeability and interstitial penetration of sterically stabilized liposomes in both normal s.c. tissue and human colon adenocarcinoma LS174T xenograft were quantified by using the dorsal skinfold chamber implanted in severe combined immunodeficient mice and intravital fluorescence microscopy. Significant extravascular accumulation was the dominant feature of liposome distribution in tumors, whereas only minimal intramural accumulation in postcapillary and collecting venules was observed in normal s.c. tissue. The extravasated liposomes in tumors distributed heterogeneously and formed perivascular clusters that did not move significantly and could be observed for up to 1 week. The effective permeability of tumor vessels to liposomes (2.0 ± 1.6 x 10-8 cm/s; n = 23) was six times smaller than that to bovine serum albumin (1.2 ± 0.5 x 10-7 cm/s; n = 6). These results provide new insights into the mechanisms of transendothelial pathways of liposomes and improvements in liposome-mediated drug delivery.
1 Supported by R35-CA-56591. Presented at the 86th Annual Meeting of American Institute of Chemical Engineers, 1993; 85th Annual Meeting of the American Association for Cancer Research, 1994; Annual Meeting of Microcirculation Society, 1994; and 42nd Annual Meeting of Radiation Research Society, 1994. M. L. was a recipient of the Feoder Lynen fellowship from the Humboldt Foundation (1991–1993). D. A. B. is a recipient of a National Research Service Award (CA59255).
Received 3/ 7/94. Accepted 5/19/94.
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