a mpeg-plga-b-pll copolymer carrier for adriamycin and sirna delivery

a amphiphilic block copolymer composed of conventional monomethoxy (polyethylene glycol)-poly (d,l-lactide-co-glycolide)-poly (l-lysine) (mpeg-plga-b-pll) was synthesized. the chemical structure of this copolymer and its precursors was confirmed by fourier transform infrared spectroscopy (ftir), ¹h nuclear magnetic resonance (¹h nmr) and gel permeation chromatography (gpc). the copolymer was used to prepare nanoparticles (nps) that were then loaded with either the anti-cancer drug adriamycin or small interfering rna-negative (sirna) using a double emulsion method. mtt assays used to study the in vitro cytotoxicity of mpeg-plga-b-pll nps showed that these particles were not toxic in huh-7 hepatic carcinoma cells. confocal laser scanning microscopy (clsm) and flow cytometer analysis results demonstrated efficient mpeg-plga-b-pll nps-mediated delivery of both adriamycin and sirna into the cells. in vivo the targeting delivery of adriamycin or sirna mediated by mpeg-plga-b-pll nps in the huh-7 hepatic carcinoma-bearing mice was evaluated using a fluorescence imaging system. the targeting delivery results and froze section analysis confirmed that drug or sirna is deliver to tumor more efficiently by mpeg-plga-b-pll nps than free drug or lipofectamine™2000. the high efficiency delivery of mpeg-plga-b-pll nps mainly due to the enhancement of cellular uptake. these results imply that mpeg-plga-b-pll nps have a great potential to be used as an effective carriers for adriamycin or sirna.