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.
Thomas
Tommy T
TT
Department of Biomedical Engineering, University of Alabama, Birmingham, Alabama 35294, USA.
Kohane
Daniel S
DS
Wang
Audrey
A
Langer
Robert
R
D000818:Animals; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D006801:Humans; D007376:Interleukin-2 / Q000737:chemistry* / Q000493:pharmacokinetics*; D051379:Mice; D010316:Particle Size
D002214:Capsules; D003692:Delayed-Action Preparations; D007376:Interleukin-2