Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Int J Pharm. 2014 Jun 5;467(1-2):123-38. doi: 10.1016/j.ijpharm.2014.03.033. Epub 2014 Mar 28.
A novel folate (FA) conjugated poly(l-γ-glutamyl glutamine) (PGG) nanoparticle loaded with docetaxel (DTX) was prepared to take advantage of both targeted drug delivery in breast cancer and reducing the overall side effects due to the adjuvant free formulation in comparison with Taxotere(®). Nanoprecipitation method was employed to prepare nanoparticles (NPs). The chemical structure of PGG synthesized polymers and PGG-FA conjugates and polymeric nanoparticles were characterized by H NMR, FTIR spectroscopy, field emission scanning electron microscopy, and laser scanning confocal microscopy. The average size of optimized nanoparticles with the aid of Box-Behnken experimental design was 131.96 ± 5.34(nm) with polydispersity of 0.089 ± 0.019, zeta potential of -25.8 ± 2.21(mV), and entrapment efficiency of 67.83 ± 3.29(%). In vitro cytotoxicity of the designed NPs was investigated by MTT assay against three chosen cell lines of MCF7, 4T1, and A549 based on their folate receptor expression capacity and was compared with Taxotere(®). Moreover, PGG-FOL NPs were loaded with 6-coumarin for cellular uptake investigation. In order to assess the antitumor efficacy and biodistribution of targeted NPs, 4T1 murine breast tumors were established on the balb/c mice and in vivo studies were performed. The obtained results showed that the novel designed system was highly effective against tumor cells and successfully localized in the tumor site.
一种新型叶酸（FA）偶联聚（L-γ-谷氨酰谷氨酰胺）（PGG）载多西紫杉醇（DTX）纳米粒被制备出来，利用其在乳腺癌中的靶向药物递送优势，并与 Taxotere(®) 相比减少由于无佐剂配方引起的总体副作用。采用纳米沉淀法制备纳米粒（NPs）。通过 1H NMR、FTIR 光谱、场发射扫描电子显微镜和激光扫描共聚焦显微镜对合成聚合物和 PGG-FA 缀合物以及聚合物纳米粒的化学结构进行了表征。在 Box-Behnken 实验设计的帮助下，优化后的纳米粒的平均粒径为 131.96±5.34(nm)，多分散指数为 0.089±0.019，zeta 电位为-25.8±2.21(mV)，包封效率为 67.83±3.29(%)。基于三种选定的细胞系 MCF7、4T1 和 A549 的叶酸受体表达能力，通过 MTT 测定法研究了设计的 NPs 的体外细胞毒性，并与 Taxotere(®) 进行了比较。此外，将 PGG-FOL NPs 负载 6-香豆素以进行细胞摄取研究。为了评估靶向 NPs 的抗肿瘤功效和生物分布，在 balb/c 小鼠上建立了 4T1 鼠乳腺癌，并进行了体内研究。结果表明，新型设计的系统对肿瘤细胞具有高度的有效性，并成功定位于肿瘤部位。
