Wang Yin-Song, Jiang Qian, Li Rong-Shan, Liu Ling-Long, Zhang Qi-Qing, Wang Yu-Mei, Zhao Jing
College of Pharmacy, Tianjin Medical University, No. 22 Qixiangtai Road, Heping District, Tianjin 300070, People's Republic of China.
Nanotechnology. 2008 Apr 9;19(14):145101. doi: 10.1088/0957-4484/19/14/145101. Epub 2008 Mar 4.
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.
本研究制备了胆固醇修饰的O-羧甲基壳聚糖（CCMC）自组装纳米颗粒，用作紫杉醇（PTX）的新型载体。通过胆固醇与O-羧甲基壳聚糖以琥珀酰键共价结合合成了CCMC-6.9，胆固醇部分的取代度（DS）为6.9%。CCMC-6.9在水性介质中形成尺寸为209.5 nm的自组装纳米颗粒。采用透析法制备了载紫杉醇的CCMC-6.9自组装纳米颗粒，并通过动态激光光散射（LLS）、透射电子显微镜（TEM）和紫外光谱（UV）对其特性进行了分析。载PTX的CCMC-6.9自组装纳米颗粒几乎呈球形，随着PTX负载量从18.7%增加到34.9%，其尺寸从245.6 nm增加到355.3 nm。采用动态透析法研究了PTX从CCMC-6.9自组装纳米颗粒中的体外释放。PTX在37℃的磷酸盐缓冲盐水（PBS）溶液中持续释放84小时，其释放对释放介质的pH敏感。在雌性Balb/c小鼠中研究了载PTX的CCMC-6.9自组装纳米颗粒的生物分布。与聚氧乙烯蓖麻油（Cremophor EL）/乙醇溶液中的PTX（PTX-Cre）相比，CCMC-6.9自组装纳米颗粒显著增加了PTX在血浆、肝脏和脾脏中的摄取，但降低了在心脏和肾脏中的摄取。这些结果表明，CCMC-6.9自组装纳米颗粒可以有效地溶解PTX并改变其组织生物分布，这可能有利于提高治疗指数并降低PTX的毒性。
