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Differential Disposition of Soluble and Liposome-Formulated Human Recombinant Interleukin-7: Effects on Blood Lymphocyte Population in Guinea Pigs

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Abstract

The effects of liposome formulation on interleukin-7 (IL-T)-dependent lymphopoietic activity was investigated based on the pharmacokinetics and tissue distribution profile of soluble and liposome-formulated recombinant human IL-7. Using 125I-IL-7, we determined the role of liposome formulation on in vivoIL-7 disposition by analyzing injection site, blood, tissue, and urinary kinetics. Following a 30- to 40-µg subcutaneous dose of soluble IL-7, most of the IL-7 was eliminated through urinary excretion within 24 hr. An equivalent subcutaneous dose of liposome-encapsulated IL-7 resulted in a peak level less than one-tenth that seen with soluble drug but produced sustained blood and urinary levels for 5 days. The bioavailability of liposome-encapsulated IL-7 was comparable to that of soluble IL-7, as determined by both blood and urinary data. Kinetic analysis of IL-7 at the subcutaneous injection site indicated that liposome encapsulation significantly reduced the rate of disappearance at the injection site. Studies with a mixture of 40% liposome-encapsulated and 60% soluble IL-7 gave an intermediate response between that of soluble IL-7 and that of liposome-encapsulated IL-7. Characterization of blood cells from IL-7-treated animals indicated that treatment with two weekly doses of mixed IL-7 liposomes (40% liposome encapsulated IL-7) significantly increased the total numbers of lymphocytes by day 14. In contrast, animals treated with soluble IL-7 on an identical dose and schedule did not produce any effect on blood lymphocytes. Collectively, liposome formulation provided a lower, but significantly sustained blood IL-7 level that enhanced IL-7 effects on blood lymphocyte numbers.

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Authors and Affiliations

  1. Department of Pharmaceutics, University of Washington, School of Pharmacy, Seattle, Washington, 98195

    Tot Bui & Rodney J. Y. Ho

  2. Department of Immunopharmacology, Sterling Winthrop Pharmaceuticals Research Division, Collegeville, Pennsylvania

    Connie Faltynek

Authors
  1. Tot Bui
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  2. Connie Faltynek
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  3. Rodney J. Y. Ho
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Bui, T., Faltynek, C. & Ho, R.J.Y. Differential Disposition of Soluble and Liposome-Formulated Human Recombinant Interleukin-7: Effects on Blood Lymphocyte Population in Guinea Pigs. Pharm Res 11, 633–641 (1994). https://doi.org/10.1023/A:1018955708443

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