Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft.

TLDR

The study quantified microvascular permeability and interstitial penetration of sterically stabilized liposomes in normal subcutaneous tissue and LS174T xenograft tumors using a dorsal skin‑fold chamber in SCID mice and intravital fluorescence microscopy. In tumors, liposomes accumulated predominantly extravascularly, forming heterogeneous perivascular clusters that persisted for up to a week, whereas only minimal extravasation occurred in normal subcutaneous tissue; the tumor vessel permeability to liposomes was six times lower than to bovine serum albumin, highlighting transendothelial pathways that could inform improved liposome‑mediated drug delivery.

Abstract

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 skin-fold 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.