Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India.
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, SAS Nagar, Mohali, Punjab, 160062, India.
Pharm Res. 2019 Sep 13;36(11):160. doi: 10.1007/s11095-019-2686-4.
Bortezomib (BTZ) is a proteasome inhibitor used for multiple myeloma and mantle cell lymphoma treatment. BTZ's aqueous in solubility is the main hindrance in its successful development as a commercial formulation. The main objective of the present study is to develop and characterize folic acid-glycine-poly-L-lactic acid (FA-Gly-PLA) based nanoformulation (NPs) to improve solubility and efficacy of BTZ.
BTZ loaded FA-Gly-PLA NPs were prepared and characterized for size, zeta potential, in vitro studies such as release, kinetics modeling, hemolytic toxicity, and cell line-based studies (Reactive Oxygen Species: ROS and cytotoxicity).
BTZ loaded NPs (BTZ-loaded FA-Gly-PLA) and blank NPs (FA-Gly-PLA) size, zeta, and PDI were found to be 110 ± 8.1 nm, 13.7 ± 1.01 mV, 0.19 ± 0.03 and 198 ± 9.01 nm, 8.63 ± 0.21 mV, 0.21 ± 0.08 respectively. The percent encapsulation efficiency (% EE) and percent drug loading (% DL) of BTZ loaded FA-Gly-PLA NPs was calculated to be 78.3 ± 4.1 and 12.38 ± 2.1. The Scanning Electron Microscopy (SEM) showed that NPs were slightly biconcave in shape. The in vitro release of BTZ from FA-Gly-PLA NPs resulted in the sustained manner. The prepared NPs were less hemolytic than BTZ.
BTZ loaded Gly-PLA NPs apoptotic index was found to be much higher than BTZ but lesser than BTZ loaded FA-Gly-PLA against breast cancer cell lines (MDA-MB-231). ROS intracellular assessment assay indicated that BTZ and BTZ loaded FA-Gly-PLA NPs exhibited higher ROS production. Conclusively, the BTZ loaded FA-Gly-PLA NPs were able to encapsulate more BTZ than BTZ loaded Gly-PLA NPs and were found to be more effective as per as in vitro anti-cancer effect is concerned.
硼替佐米（BTZ）是一种用于多发性骨髓瘤和套细胞淋巴瘤治疗的蛋白酶体抑制剂。BTZ 在水中的溶解度低，这是其成功开发为商业制剂的主要障碍。本研究的主要目的是开发并表征叶酸-甘氨酸-聚-L-乳酸（FA-Gly-PLA）为基础的纳米制剂（NPs），以提高 BTZ 的溶解度和疗效。
制备并表征 BTZ 负载的 FA-Gly-PLA NPs 的粒径、Zeta 电位、体外释放、动力学模型、溶血毒性和基于细胞系的研究（活性氧：ROS 和细胞毒性）。
BTZ 负载的 NPs（BTZ 负载的 FA-Gly-PLA）和空白 NPs（FA-Gly-PLA）的粒径、Zeta、PDI 分别为 110±8.1nm、13.7±1.01mV、0.19±0.03 和 198±9.01nm、8.63±0.21mV、0.21±0.08。BTZ 负载的 FA-Gly-PLA NPs 的包封效率（%EE）和载药量（%DL）分别计算为 78.3±4.1%和 12.38±2.1%。扫描电子显微镜（SEM）显示 NPs 呈稍扁双凹形。BTZ 从 FA-Gly-PLA NPs 的体外释放呈持续方式。与 BTZ 相比，制备的 NPs 的溶血作用较小。
BTZ 负载的 Gly-PLA NPs 的凋亡指数明显高于 BTZ，但低于 BTZ 负载的 FA-Gly-PLA 对乳腺癌细胞系（MDA-MB-231）的作用。ROS 细胞内评估试验表明，BTZ 和 BTZ 负载的 FA-Gly-PLA NPs 产生更高的 ROS。总之，与 BTZ 负载的 Gly-PLA NPs 相比，BTZ 负载的 FA-Gly-PLA NPs 能够包封更多的 BTZ，并且在体外抗癌效果方面表现出更高的疗效。
