Interleukin-2-containing liposomes: interaction of interleukin-2 with liposomal bilayers and preliminary studies on application in cancer vaccines.
Interleukin-2 (IL-2) incorporation in liposomes was studied under different conditions. Information was obtained on the mechanism of interaction of glycosylated recombinant IL-2 with liposomal bilayers. This information was utilized to formulate liposomes with high levels of incorporated IL-2. Multilamellar vesicles were prepared by hydration of a lipid film with an IL-2 solution. The incorporation efficiency, measured with a bioassay after forced release of IL-2 from the vesicles, was strongly dependent on the charge of the liposomes and the pH and ionic strength of the hydration medium. Negatively charged liposomes composed of phosphatidylcholine/phosphatidylglycerol (9:1) and prepared with IL-2 dissolved in 10 mM NaAc/270 mM glycerol, 0.1% BSA, pH 5, showed the highest incorporation efficiency (81%) among the investigated preparations. This type of liposome was selected for further study. Electrostatics play a crucial role in the process of IL-2 association with this type of liposome. Initial studies concerning induction of protective tumor immunity by immunization with reconstituted membranes with muramyl tripeptide phosphatidylethanolamine indicate that coinjection of IL-2-containing liposomes provided a significant enhancement of the immune response.
Bergers
J J
JJ
Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Den Otter
W
W
Dullens
H F
HF
Kerkvliet
C T
CT
Crommelin
D J
DJ
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004337:Drug Carriers; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000737:chemistry; D008081:Liposomes; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D014612:Vaccines / Q000008:administration & dosage*
D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D011994:Recombinant Proteins; D014612:Vaccines