Microparticulate formulations for the controlled release of interleukin-2.

Interleukin 2 (IL-2) is a pleotropic growth factor essential to immune system function. Current methods of administration are limited by the necessity of hospitalization as well as dose-limiting toxicities and side effects. There is also the issue of low therapeutic concentrations at the desired site of action; for instance, in the case of solid tumor treatment. Here we describe the design of controlled-release vehicles for the local administration of IL-2 based on single (SE) and double emulsion (DE) poly(lactic-co-glycolic acid) (PLGA) systems and a newly developed class of spray-dried lipid-protein-sugar systems composed of L-alpha-dipalmitoylphosphatidylcholine (DPPC) and 0.2% Eudragit E 100. All three systems demonstrated the release of therapeutic drug quantities. Totals of 2.0, 0.5, and 2.8 microg of IL-2 (per mg of solid) were encapsulated in the SE, DE, and spray-dried formulations, respectively. The SE and DE released of 30 and 15% of the encapsulated protein, respectively, with delivery of biologically active IL-2 during the first 5 to 10 days. The lipid-protein-sugar-based system demonstrated extended sustained release of biologically active IL-2 for a period of 4 months. These systems provide a potential framework for long-term loco-regional immunotherapeutic treatment regimens. Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1100-1109, 2004