We encapsulated cyclosporine A (CsA) in poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) (PEG-PLGA) nanoparticles (NPs)\r\nby nanoprecipitation of CsA and PEG-PLGA. The resulting CsA/PEG-PLGA-NPs were <100nm in diameter with a narrow\r\nparticle size distribution. The NP size could be controlled by tuning the polymer concentration, solvent, or water/solvent ratio\r\nduring formulation. The PEGylated NPs maintained non-aggregated in salt solution. Solid NPs lyoprotected with bovine serum\r\nalbumin were prepared for the convenience of storage and transportation. The release kinetics of CsA (55.6% released on Day 1)\r\nshowed potential for maintaining therapeutic CsA concentrations in vivo. In T-cell assays, both free CsA and CsA/PEG-PLGA-NPs\r\nsuppressed T-cell proliferation and production of inflammatory cytokines dose dependently. In a mixed lymphocyte reaction assay,\r\nthe IC50 values for free CsA and CsA/PEG-PLGA-NPs were found to be 30 and 35 ng/mL, respectively. This nanoparticulate CsA\r\ndelivery technology constitutes a strong basis for future targeted delivery of immunosuppressive drugs with improved efficiency\r\nand potentially reduced toxicity.
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