Enhanced Delivery System of Flutamide Loaded Chitosan-Dextran Sulphate Nanoparticles for Prostate Cancer

Abstract

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using chitosan (CS) and dextran sulphate (DS) nanoparticles and were characterized using different techniques. The prepared nanoparticles showed a size of 80-120 nm with an entrapment efficiency of 55 +/- 6.95%. In addition, blood compatibility, in vitro cytotoxicity, drug release and cellular uptake studies were also carried out. The drug release studies showed a sustained and pH dependent release pattern as a result, after 120 h about 66% drug release occurred at pH 7.4 and 78% release occurred in acidic pH. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) experiments proved the preferential toxicity of drug loaded nanoparticles towards prostate cancer cells (PC3) unlike in normal cells, mouse fibroblast cells (L929). The cell death mechanism of drug loaded nanoparticles for a concentration of 50 and 75 nM showed 28 +/- 2 and 35.2 +/- 4% apoptosis in samples treated with the PC3 cells after 24 h. Fluorescent microscopic imaging and flow cytometry confirmed the preferential uptake of the nanoparticles (NPs) in the prostate cancer cells (PC3) unlike in normal (L929) cells. Hence the developed FLT loaded CS-DS NPs could be used as a promising system for controlled delivery in prostate cancer.