State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Pharmacy College, Fujian University of Traditional Chinese Medicine, 1 Huatuo Road, Minhou Shangjie, Fuzhou 350122, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Biomaterials. 2014 Aug;35(26):7654-65. doi: 10.1016/j.biomaterials.2014.05.053. Epub 2014 Jun 11.
An amphiphilic carboxymethyl chitosan-quercetin (CQ) conjugate was designed and synthesized for oral delivery of paclitaxel (PTX) to improve its oral bioavailability by increasing its water solubility and bypassing the P-gp drug efflux pumps. CQ conjugate had low critical micelle concentration (55.14 μg/mL), and could self assemble in aqueous condition to form polymeric micelles (PMs). PTX-loaded CQ PMs displayed a particle size of 185.8 ± 4.6 nm and polydispersity index (PDI) of 0.134 ± 0.056. The drug-loading content (DL) and entrapment efficiency (EE) were 33.62 ± 1.34% and 85.63 ± 1.26%, respectively. Moreover, PTX-loaded CQ PMs displayed similar sustained-release profile in simulated gastrointestinal fluids (pH 1.2/pH 6.8) and PBS (pH 7.4). In situ intestinal absorption experiment showed that PTX-loaded CQ PMs significantly improved the effective permeability of PTX as compared to verapamil (P < 0.01). Likewise, PTX-loaded CQ PMs significantly enhanced the oral bioavailability of PTX, resulting in strong antitumor efficacy against tumor xenograft models with better safety profile as compared to Taxol(®) and Taxol(®) with verapamil. Overall, the results implicate that CQ PMs are promising vehicles for the oral delivery of water-insoluble anticancer drugs.
一种两亲性羧甲基壳聚糖-槲皮素（CQ）缀合物被设计并合成用于紫杉醇（PTX）的口服递送，以通过增加其水溶性并绕过 P-糖蛋白药物外排泵来提高其口服生物利用度。CQ 缀合物具有低临界胶束浓度（55.14μg/mL），并且可以在水条件下自组装形成聚合物胶束（PM）。载紫杉醇的 CQ PM 的粒径为 185.8±4.6nm，多分散指数（PDI）为 0.134±0.056。药物载量（DL）和包封效率（EE）分别为 33.62±1.34%和 85.63±1.26%。此外，载紫杉醇的 CQ PM 在模拟胃肠道液（pH 1.2/pH 6.8）和 PBS（pH 7.4）中表现出相似的持续释放特征。原位肠吸收实验表明，与维拉帕米相比，载紫杉醇的 CQ PM 显著提高了紫杉醇的有效渗透性（P<0.01）。同样，载紫杉醇的 CQ PM 显著提高了紫杉醇的口服生物利用度，与 Taxol（®）和 Taxol（®）联合维拉帕米相比，具有更好的安全性，对肿瘤异种移植模型具有更强的抗肿瘤疗效。总体而言，结果表明 CQ PM 是用于递送水不溶性抗癌药物的有前途的载体。
