Nanoparticles based on chitosan hydrochloride/hyaluronic acid/PEG containing curcumin: In vitro evaluation and pharmacokinetics in rats

Nanoparticles based on chitosan hydrochloride (CSH)-hyaluronic acid (HA)-PEG were prepared for delivering curcumin (CUR) (CUR-PNPs) to brain tumor. CUR-PNPs of 245.9   nm and spherical morphology were obtained at optimized CSH/HA/PEG20000/CUR ratios with negative charge of about −27.2   mV and EE of approximately 93.3%. Cytotoxicity studies showed that CUR-PNPs improved drug’s anticancer activity in rat glioma cells (C6). The cellular uptake mechanism study showed active targeting of CUR-PNPs into C6 cells by HA mediated endocytosis . Clathrin-coated pit mediated endocytosis, clathrin-mediated endocytosis and macropincytosis were also identified as the entry pathways of PNPs into C6 cells. Pharmacokinetics of preparations in rats after i.v. administration further proved the superiority of CUR-PNPs (3.98 times greater than the area under the curve of CUR solution). In conclusion, CUR-PNPs might be a promising carrier for the therapy of brain tumors.