title: Self-assembled nanoparticles of cholesterol-modified O-carboxymethyl chitosan as a novel carrier for paclitaxel.
abstract: Self-assembled nanoparticles of cholesterol-modified O-carboxymethyl chitosan (CCMC) were prepared to be used as a novel carrier for paclitaxel (PTX) in this study. CCMC-6.9 was synthesized by the covalent conjugation of cholesterol to O-carboxymethyl chitosan with the succinyl linkage and the degree of substitution (DS) of the cholesterol moiety was 6.9%. CCMC-6.9 formed self-assembled nanoparticles with a size of 209.5 nm in aqueous media. Paclitaxel-loaded CCMC-6.9 self-assembled nanoparticles were prepared using a dialysis method and their characteristics were analyzed by dynamic laser light scattering (LLS), transmission electron microscopy (TEM) and ultraviolet spectroscopy (UV). PTX-loaded CCMC-6.9 self-assembled nanoparticles were almost spherical in shape and their size increased from 245.6 to 355.3 nm with PTX-loading content increasing from 18.7% to 34.9%. In vitro release of PTX from CCMC-6.9 self-assembled nanoparticles was carried out by the dynamic dialysis method. PTX continuously released in phosphate buffered saline (PBS) solutions for 84 h at 37 °C and its release was sensitive to the pH of the release media. The biodistribution of PTX-loaded CCMC-6.9 self-assembled nanoparticles was studied in female Balb/c mice. Compared with PTX in the solution of Cremophor EL (polyethoxylated castor oil)/ethanol (PTX-Cre), CCMC-6.9 self-assembled nanoparticles significantly increased the uptake of PTX in plasma, liver and spleen, but decreased the uptake in heart and kidney. These results suggest that CCMC-6.9 self-assembled nanoparticles can effectively solubilize PTX and modify its tissue biodistribution, which may be advantageous in enhancing the therapeutic index and reducing the toxicity of PTX.
authors.affiliation: College of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
authors.forename: Yin-Song
authors.initials: YS
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Rong-Shan
authors.initials: RS
authors.lastname: Li
authors.forename: Ling-Long
authors.initials: LL
authors.lastname: Liu
authors.forename: Qi-Qing
authors.initials: QQ
authors.lastname: Zhang
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao