Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India.
Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, New Delhi, 110054, India.
Pharm Res. 2018 Aug 31;35(11):200. doi: 10.1007/s11095-018-2482-6.
Bendamustine is an important drug for the treatment of chronic lymphatic leukaemia (CLL), non-Hodgkin lymphoma (NHL). However, its delivery is challenging due to its instability. Current approach reports the development and characterization of bendamustine encapsulated PLGA nanoparticles for the effective targeting to leukemic cells.
The prepared, bendamustine loaded PLGA nanoparticles (BLPNP) were developed and characterized for particle size, zeta potential and polydispersity index. The formed nanoparticles were further characterized with the help of electron microscopy for surface morphology. The formed nanoparticles were evaluated for cytotoxicity, cell uptake, ROS and cell apoptosis against THP-1 leukemic cells as a part of in vitro evaluation. In vivo organ bio-distribution and tumor regression studies were performed to track in vivo behaviour of BLPNP.
The average particle size was 138.52 ± 3.25 nm, with 0.192 ± 0.036 PDI and - 25.4 ± 1.38 mV zeta potential. TEM images revealed the homogeneous particle size distribution with uniform shape. In vitro release exhibited a sustained drug-release behaviour up to 24 h. Cytotoxicity against THP-1 cells through MTT assay observed IC value of 27.8 ± 2.1 μM for BLPNP compared to pure drug, which was 50.42 ± 3.4 μM. Moreover, in vitro studies like cell-uptake and cell apoptosis studies further confirmed the higher accumulation of BLPNP in comparison to the pure drug. Organ distribution and tumor regression studies were performed to track in vivo behaviour of bendamustine loaded nanoparticles.
The overall study described a promising approach in terms of safety, least erythrocytic toxicity, better IC value with enhance tumor targeting and regression.
苯达莫司汀是治疗慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL）的重要药物。然而，由于其不稳定性，其输送具有挑战性。目前的方法报告了载有苯达莫司汀的 PLGA 纳米粒的开发和特性，以实现对白血病细胞的有效靶向。
制备了载有苯达莫司汀的 PLGA 纳米粒（BLPNP），并对其粒径、zeta 电位和多分散指数进行了评价。借助电子显微镜对形成的纳米粒进行了表面形态学的进一步表征。通过体外评价，对 THP-1 白血病细胞的细胞毒性、细胞摄取、ROS 和细胞凋亡进行了评价。进行了体内器官生物分布和肿瘤回归研究，以跟踪 BLPNP 的体内行为。
平均粒径为 138.52±3.25nm，PDI 为 0.192±0.036，zeta 电位为-25.4±1.38mV。TEM 图像显示了均匀的粒径分布和均匀的形状。体外释放表现出长达 24 小时的持续药物释放行为。通过 MTT 法测定对 THP-1 细胞的细胞毒性，BLPNP 的 IC 值为 27.8±2.1μM，而纯药物的 IC 值为 50.42±3.4μM。此外，细胞摄取和细胞凋亡等体外研究进一步证实了 BLPNP 的积累量明显高于纯药物。进行了器官分布和肿瘤回归研究，以跟踪载有苯达莫司汀的纳米粒的体内行为。
总体研究描述了一种有前途的方法，具有安全性高、红细胞毒性最小、IC 值更好、肿瘤靶向性增强和肿瘤消退的优点。
