Karaelmas University, Chemistry Department, Physical Chemistry Division, Zonguldak, Turkey.
Eur J Pharm Sci. 2011 Oct 9;44(3):310-20. doi: 10.1016/j.ejps.2011.08.013. Epub 2011 Aug 23.
Targeted drug delivery systems are one of the most promising alternatives for the cancer therapy. Rapid developments on nanomedicine facilitated the creation of novel nanotherapeutics by using different nanomaterials. Especially polymer based nanoparticles are convenient for this purpose. In this study; a natural polymer (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHHX) was used as a base matrix for the production of a novel nanotherapeutic including antineoplastic agent, Etoposide and attached folic acid as a ligand on the nanoparticles. Modified solvent evaporation technique was used for the production of PHBHHX nanoparticles and the average size of the obtained PHBHHX nanoparticles were observed in the range of 180 nm and 1.5 μm by the change in experimental conditions (i.e., homogenization rate, surfactant concentration and polymer/solvent ratio). By the increase in homogenization rate and surfactant concentration, size of the nanoparticles was decreased, while the size was increased by the increase in polymer/solvent ratio. Drug loading ratio was also found to be highly affected by polymer/drug ratio. Surface charge of the prepared nanoparticles was also investigated by zeta potential measurements. In the cytotoxicity tests; Etoposide loaded and folic acid attached PHBHHX nanoparticles were observed as more effective on HeLa cells than Etoposide loaded PHBHHX nanoparticles without attached folic acid. The cytotoxicity of folic acid conjugated PHBHHX nanoparticles to cancer cells was found to be much higher than that of normal fibroblast cells, demonstrating that the folate conjugated nanoparticles has the ability to selectively target to cancer cells. In addition, apoptotic/necrotic activities were evaluated for all formulations of the PHBHHX nanoparticles and parallel results with cytotoxicity tests were obtained. These studies demonstrate that the folic acid attached and Etoposide loaded PHBHHX nanoparticles seem as promising for the targeted cancer therapy.
靶向药物输送系统是癌症治疗最有前途的方法之一。纳米医学的快速发展促进了新型纳米治疗剂的创建，使用了不同的纳米材料。特别是基于聚合物的纳米粒子在这方面很方便。在本研究中；使用天然聚合物（聚（3-羟基丁酸-co-3-羟基己酸），PHBHHX）作为基础基质，用于生产包括抗肿瘤剂依托泊苷和附着叶酸作为配体的新型纳米治疗剂。改良溶剂蒸发技术用于生产 PHBHHX 纳米粒子，通过改变实验条件（即均化速率、表面活性剂浓度和聚合物/溶剂比），观察到获得的 PHBHHX 纳米粒子的平均粒径在 180nm 和 1.5μm 范围内。通过增加均化速率和表面活性剂浓度，可以减小纳米粒子的尺寸，而通过增加聚合物/溶剂比，可以增加纳米粒子的尺寸。载药率也被发现高度受聚合物/药物比的影响。还通过ζ电位测量研究了制备的纳米粒子的表面电荷。在细胞毒性试验中；与未附着叶酸的载依托泊苷 PHBHHX 纳米粒子相比，负载依托泊苷和附着叶酸的 PHBHHX 纳米粒子对 HeLa 细胞更有效。叶酸偶联 PHBHHX 纳米粒子对癌细胞的细胞毒性被发现比正常成纤维细胞高得多，表明叶酸偶联纳米粒子具有选择性靶向癌细胞的能力。此外，还评估了所有 PHBHHX 纳米粒子制剂的凋亡/坏死活性，并获得了与细胞毒性试验平行的结果。这些研究表明，叶酸偶联和载依托泊苷 PHBHHX 纳米粒子似乎是有前途的靶向癌症治疗方法。
