Potential usage of thermosensitive liposomes for site-specific delivery ofcytokines

Long-circulating liposomes reside long in the bloodstream, and transient sw elling during phase transition of liposomes with hyper-osmotic internal aqu eous phase causes release of macromolecules. Here we examined the applicabi lity of long-circulating thermosensitive liposomes for delivery of tumor ne crosis factor (TNF) by the heating of a local tumor-growing site after inje ction of TNF-loaded liposomes into tumor-bearing mice. Glucuronate modified thermosensitive liposomes with internal solution of two-fold higher osmoti c pressure and sized through 200 nm-pore, released encapsulated [I-131] hum an serum albumin at 42 degreesC in vitro and showed long-circulating charac ter in vivo. Cytotoxic action of TNF encapsulated in long-circulating therm osensitive-liposomes (LCTS-liposomes) against L929 fibrosarcoma cells was e nhanced at 42 degreesC in vitro. Furthermore, the tumor growth tended to be inhibited more by hyperthermia of mice bearing Meth A sarcoma than without hearing after injection of TNF encapsulated in LCTS-liposomes. These resul ts suggest that the cytokine can be released at the turner site from the ci rculating LCTS-liposomes. (C) 2000 Published by Elsevier Science Ireland Lt d. All rights reserved.