Interleukin-2 lipid microspheres. I. development and evaluation of the colloidal drug carrier

Abstract

Undesirable toxic effects associated with intravenous interleukin-2 (IL2) therapy have limited its use for the treatment of cancer. Therefore, we investigated properties of a colloidal carrier system intended for the delivery of IL2. Lipid microspheres (LMS) are 10% (v/v) soybean oil emulsions stabilized with block copolymers of the poloxamer and poloxamine type. Poloxamers 238,338,407 or poloxamine 908 LMS were evaluated for physical stability, in uitro toxicity, and in viuo biodistribution. With the exception of 2% poloxamer 238 LMS, all preparations displayed acceptable stability when stored for 3 months at 4" or 37°C. In addition, all LMS preparations exhibited physical stability when subjected to freezethaw cycling and extended periods of freezing. In uitro cellular toxicity was evaluated in a murine cytotoxic T lymphocyte cell line (CTLL-2) and human peripheral blood mononuclear cells (PBMC). The calculated ICs0 of LMS was approximately 30 and 10 mg/liter in CTLL-2 cells and PBMC, respectively. Biodistribution studies involving 12sI-labeled LMS revealed that 2 h after intravenous administration there was significantly greater recovery of the poloxamer 338 and 407 LMSassociated radioactivity, where blood, liver, spleen, and bone marrow accounted for most of the radioactivity. Overall, the data suggest that LMS have the potential to serve as a drug delivery system. o