College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam 534-729, Republic of Korea.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Int J Pharm. 2015 Jul 5;488(1-2):70-7. doi: 10.1016/j.ijpharm.2015.04.046. Epub 2015 Apr 18.
Poly(D,L-lactic acid)-glycerol (PDLLA-G)-based nanoparticles (NPs) were fabricated for the intravenous delivery of curcumin (CUR). NPs with a mean diameter of approximately 200 nm, a narrow size distribution, and capable of efficient drug encapsulation were prepared using an emulsification-solvent evaporation method. The stability of NPs was verified in water, phosphate buffered saline (PBS), and serum after 24-h incubation. A sustained drug release pattern was observed, and the amount of CUR released in acidic media (pH 5.5) was higher than in media at physiological pH (pH 7.4). Blank NPs (without drug loading) did not exhibit severe cytotoxicity in MDA-MB-231 human breast adenocarcinoma cells. The in vitro anti-tumor efficacy of CUR-loaded NPs in MDA-MB-231 cells was comparable to that of a solution of CUR. Pharmacokinetic studies in rats showed that the in vivo clearance (CL) of CUR in the NP-treated group was lower than the group treated with CUR solution. Therefore, encapsulation of CUR in PDLLA-G NPs was shown to enable prolonged circulation of the drug in the blood stream and guarantee improved anticancer activity after intravenous injection. These biocompatible NPs could be an efficient nano-sized injectable formulation for CUR delivery.
聚(D,L-乳酸)-甘油(PDLLA-G)为基础的纳米粒子(NPs)被用于姜黄素(CUR)的静脉给药。采用乳化-溶剂蒸发法制备平均直径约为 200nm、粒径分布窄、能够高效包封药物的 NPs。在水、磷酸盐缓冲盐水(PBS)和血清中孵育 24 小时后,验证了 NPs 的稳定性。观察到了持续的药物释放模式,在酸性介质(pH5.5)中释放的 CUR 量高于生理 pH(pH7.4)介质中的量。空白 NPs(无药物负载)在 MDA-MB-231 人乳腺癌腺癌细胞中没有表现出严重的细胞毒性。载 CUR 的 NPs 在 MDA-MB-231 细胞中的体外抗肿瘤功效与 CUR 溶液相当。大鼠的药代动力学研究表明,NP 处理组中 CUR 的体内清除率(CL)低于 CUR 溶液处理组。因此,将 CUR 包封在 PDLLA-G NPs 中可使药物在血液中的循环时间延长,并保证静脉注射后抗肿瘤活性的提高。这些生物相容性 NPs 可能是一种有效的 CUR 纳米级注射制剂。