Biodistribution and tumor localization of stealth liposomal tumor necrosis factor-α in soft tissue sarcoma bearing rats

Alexander H. Van der Veen, Alexander M.M. Eggermont, Ann L.B. Seynhaeve, Sandra T. Van Tiel, Timo L.M. Ten Hagen

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

57 Citaten (Scopus)


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 67gallium-desferal, as well as the blood concentration of soluble TNF-α and liposome encapsulated TNF-α using 125I. 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.

Originele taal-2Engels
Pagina's (van-tot)901-906
Aantal pagina's6
TijdschriftInternational Journal of Cancer
Nummer van het tijdschrift6
StatusGepubliceerd - 1998
Extern gepubliceerdJa


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