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Biodistribution and tumor localization of stealth liposomal tumor necrosis factor‐α in soft tissue sarcoma bearing rats
Author(s) -
van der Veen Alexander H.,
Eggermont Alexander M. M.,
Seynhaeve Ann L. B.,
van Tiel Sandra T.,
ten Hagen Timo L. M.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980911)77:6<901::aid-ijc17>3.0.co;2-3
Subject(s) - liposome , biodistribution , tumor necrosis factor alpha , mononuclear phagocyte system , pharmacokinetics , spleen , cytokine , chemistry , pharmacology , medicine , peripheral blood mononuclear cell , immunology , biochemistry , in vitro
The blood residence half‐life and organ distribution of recombinant human tumor necrosis factor‐α (TNF‐α) encapsulated in sterically stabilized liposomes, were investigated in rats bearing a soft tissue sarcoma in the hind leg. We studied the decay in blood concentration of “empty” liposomes using the aqueous marker 67 gallium‐desferal, as well as the blood concentration of soluble TNF‐α and liposome encapsulated TNF‐α using 125 I. Encapsulation efficacy of TNF‐α was 24%. The pharmacokinetics of TNF‐α were markedly altered after encapsulation in liposomes, with a 33‐fold increase in mean residence time of TNF‐α in the blood, and a concomitant 14‐fold increase in the area under the plasma concentration vs. time curve for liposomal TNF‐α. Although the liposomes exhibit Stealth characteristics, uptake by mononuclear phagocyte‐rich organs ( e.g. , liver and spleen) was noticeable, especially at later time points. Encapsulation of TNF‐α in sterically stabilized liposomes resulted in a marked increase in localization of the cytokine in tumor measured as total uptake over time. However, peak TNF‐α concentration levels in tumor were not significantly enhanced compared with free TNF‐α. Besides the augmented localization of TNF‐α after encapsulation in sterically stabilized liposomes, a diminished toxicity was observed. Int. J. Cancer 77:901–906, 1998.© 1998 Wiley‐Liss, Inc.