Potential usage of thermosensitive liposomes for site-specific delivery of cytokines.
Long-circulating liposomes reside long in the bloodstream, and transient swelling during phase transition of liposomes with hyper-osmotic internal aqueous phase causes release of macromolecules. Here we examined the applicability of long-circulating thermosensitive liposomes for delivery of tumor necrosis factor (TNF) by the heating of a local tumor-growing site after injection of TNF-loaded liposomes into tumor-bearing mice. Glucuronate modified thermosensitive liposomes with internal solution of two-fold higher osmotic pressure and sized through 200 nm-pore, released encapsulated [(131)I] human serum albumin at 42 degrees C in vitro and showed long-circulating character in vivo. Cytotoxic action of TNF encapsulated in long-circulating thermosensitive-liposomes (LCTS-liposomes) against L929 fibrosarcoma cells was enhanced at 42 degrees C in vitro. Furthermore, the tumor growth tended to be inhibited more by hyperthermia of mice bearing Meth A sarcoma than without heating after injection of TNF encapsulated in LCTS-liposomes. These results suggest that the cytokine can be released at the tumor site from the circulating CLTS-liposomes.
Yuyama
Y
Y
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka, Japan.
Tsujimoto
M
M
Fujimoto
Y
Y
Oku
N
N
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000008:administration & dosage*; D005965:Glucuronates / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008081:Liposomes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000378:metabolism; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy; D012709:Serum Albumin / Q000378:metabolism; D013696:Temperature; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D016207:Cytokines; D005965:Glucuronates; D008081:Liposomes; D011994:Recombinant Proteins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha