MICROVASCULAR PERMEABILITY AND INTERSTITIAL PENETRATION OF STERICALLYSTABILIZED (STEALTH) LIPOSOMES IN A HUMAN TUMOR XENOGRAFT

Microvascular permeability and interstitial penetration of sterically stabilized liposomes in both normal s.c. tissue and human colon adenoc arcinoma LS174T xenograft were quantified by using the dorsal skinfold chamber implanted in severe combined immunodeficient mice and intravi tal fluorescence microscopy. Significant extravascular accumulation wa s the dominant feature of liposome distribution in tumors, whereas onl y minimal intramural accumulation in postcapillary and collecting venu les was observed in normal s.c. tissue. The extravasated liposomes in tumors distributed heterogeneously and formed perivascular clusters th at 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 liposome s and improvements in liposome-mediated drug delivery.