Guan Qingxiang, Sun Dandan, Zhang Guangyuan, Sun Cheng, Wang Miao, Ji Danyang, Yang Wei
Department of Pharmaceutics, School of Pharmacy, Jilin University, No. 1266, Fujin Road, Changchun 130021, China.
Department of Neurology, Second Hospital of Jilin University, Changchun 130041, China.
Molecules. 2016 Dec 2;21(12):1641. doi: 10.3390/molecules21121641.
Poorly soluble drugs have low bioavailability after oral administration, thereby hindering effective drug delivery. A novel drug-delivery system of docetaxel (DTX)-based stearic acid (SA)-modified polysaccharides (BSPs) copolymers was successfully developed. Particle size, potential, encapsulation efficiency (EE), and loading capacity (LC) were determined. The DTX release percentage in vitro was determined using high performance liquid chromatography (HPLC). The hemolysis and in vitro anticancer activity were studied. Cellular uptake and apoptotic rate were measured using flow cytometry assay. Particle size, potential, EE and LC were 125.30 ± 1.89 nm, -26.92 ± 0.18 mV, 86.6% ± 0.17%, and 14.8% ± 0.13%, respectively. The anticancer activities of DTX-SA-BSPs copolymer micelles against HepG2, HeLa, SW480, and MCF-7 (83.7% ± 1.0%, 54.5% ± 4.2%, 48.5% ± 4.2%, and 59.8% ± 1.4%, respectively) were superior to that of docetaxel injection (39.2% ± 1.1%, 44.5% ± 5.3%, 38.5% ± 5.4%, and 49.8% ± 2.9%, respectively) at 0.5 μg/mL drug concentration. The DTX release percentage of DTX-SA-BSPs copolymer micelles and docetaxel injection were 66.93% ± 1.79% and 97.06% ± 1.56% in two days, respectively. Cellular uptake of DTX-FITC-SA-BSPs copolymer micelles in cells had a time-dependent relation. Apoptotic rate of DTX-SA-BSPs copolymer micelles and docetaxel injection were 73.48% and 69.64%, respectively. The SA-BSPs copolymer showed good hemocompatibility. Therefore, SA-BSPs copolymer can be used as a carrier for delivering hydrophobic drugs.
难溶性药物口服给药后生物利用度低，从而阻碍了有效的药物递送。一种基于多西他赛（DTX）的硬脂酸（SA）修饰多糖（BSPs）共聚物的新型药物递送系统被成功开发出来。测定了粒径、电位、包封率（EE）和载药量（LC）。使用高效液相色谱法（HPLC）测定了多西他赛在体外的释放率。研究了溶血情况和体外抗癌活性。使用流式细胞术测定细胞摄取和凋亡率。粒径、电位、EE和LC分别为125.30±1.89nm、-26.92±0.18mV、86.6%±0.17%和14.8%±0.13%。在药物浓度为0.5μg/mL时，DTX-SA-BSPs共聚物胶束对HepG2、HeLa、SW480和MCF-7细胞的抗癌活性（分别为83.7%±1.0%、54.5%±4.2%、48.5%±4.2%和59.8%±1.4%）优于多西他赛注射液（分别为39.2%±1.1%、44.5%±5.3%、38.5%±5.4%和49.8%±2.9%）。DTX-SA-BSPs共聚物胶束和多西他赛注射液在两天内的多西他赛释放率分别为66.93%±1.79%和97.06%±1.56%。细胞对DTX-FITC-SA-BSPs共聚物胶束的摄取具有时间依赖性。DTX-SA-BSPs共聚物胶束和多西他赛注射液的凋亡率分别为73.48%和69.64%。SA-BSPs共聚物表现出良好的血液相容性。因此，SA-BSPs共聚物可作为递送疏水性药物的载体。
