Cytotoxicity and cellular uptake evaluation of mitoxantrone-loaded poly(lactic acid-co-lysine) arginine-glycine-aspartic acid nanoparticles

The purpose of this study was to evaluate the in vitro characteristics of poly(lactic acid-co-lysine) arginine-glycine-aspartic acid (PLA-PLL-RGD) nanoparticles (NPs) loaded with mitoxantrone. PLA-PLL-RGD NPs with a particle size of 200 nm were prepared with a modified emulsification solvent-diffusion method. The encapsulation efficiency of the mitoxantrone-loaded NPs was 85%. In vitro release experiments showed that the release of the drug was prolonged and sustained, and approximately 60.2% of the mitoxantrone was released in the first week. The released drug was integrated to achieve desired drug-release profiles and still possessed bioactivity according to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2h-tetrazolium bromide assay, which indicated that mitoxantrone-loaded NPs were more cytotoxic against Michigan Cancer Foundation 7 (MCF-7) breast cancer cells than mitoxantrone. Furthermore, the association processes of NPs with MCF-7 cells, including binding and effective internalization, were investigated in vitro. The cellular uptake of the NPs was qualitatively studied with confocal laser scanning microscopy and was confirmed with flow cytometry analysis. These experimental results indicated that PLA-PLL-RGD NPs could be used as drug carriers for mitoxantrone. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 119: 1011-1015, 2011