Differential disposition of soluble and liposome-formulated human recombinant interleukin-7: effects on blood lymphocyte population in guinea pigs.
The effects of liposome formulation on interleukin-7 (IL-7)-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 vivo IL-7 disposition by analyzing injection site, blood, tissue, and urinary kinetics. Following a 30- to 40-microgram 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bui
T
T
Department of Pharmaceutics, University of Washington, School of Pharmacy, Seattle 98195.
Faltynek
C
C
Ho
R J
RJ
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D004337:Drug Carriers; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007279:Injections, Subcutaneous; D015851:Interleukin-7 / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007958:Leukocyte Count / Q000187:drug effects; D008081:Liposomes; D008214:Lymphocytes / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
D004337:Drug Carriers; D015851:Interleukin-7; D007457:Iodine Radioisotopes; D008081:Liposomes; D011994:Recombinant Proteins