a Biochemistry Department, Faculty of Medicine , Lorestan University of Medical Science , Khorramabad , Iran.
b Social Medicine Department, Faculty of Medicine , Lorestan University of Medical Sciences , Khorramabad , Iran.
Drug Dev Ind Pharm. 2018 Aug;44(8):1371-1376. doi: 10.1080/03639045.2018.1451880. Epub 2018 Apr 11.
Vinblastine (VB), as a chemotherapeutic agent, is widely used in treatment of different types of cancer. However, its clinical application is limited due to its low water solubility, side effects, and multidrug resistance. The aim of this study was to increase the therapeutic efficacy of VB using drug delivery systems. For this purpose, a PEGylated niosomal formulation of vinblastine (Pn-VB) was prepared by thin film hydration method and physicochemically characterized. Drug release pattern was performed by dialysis diffusion method. The cytotoxicity of Pn-VB was investigated against murine lung cancer TC-1 cells using MTT assay and its tumor inhibitory effect was evaluated in lung tumor-bearing C57BL/6 mice. Mean particle size, zeta potential, entrapment, and loading efficiency of niosomes were obtained to be about 234.3 ± 11.4 nm, -34.6 ± 4.2 mV, 99.92 ± 1.6%, and 2.673 ± 0.30%, respectively. While, the mean particle size and zeta potential for non-PEGylated niosomes were obtained about 212.4 nm and -31.4 mV, respectively. The in vitro release pattern of drug from niosomes showed a sustained release behavior. Pn-VB indicated a significant increase in toxicity against TC-l cells as compared to free VB. In animal model, Pn-VB exhibited stronger tumor inhibitory effect and longer life time in comparison to free VB. In conclusion, Pn-VB showed appropriate stability, high-entrapment efficacy, lower releasing rate, and stronger cytotoxic activity against lung cancer TC-1 cells as compared to free drug. Thus, the Pn-VB could be a promising formulation for delivery of vinblastine to tumor cells with enhanced drug bioavailability and therapeutic efficacy.
长春碱（VB）作为一种化疗药物，广泛用于治疗不同类型的癌症。然而，由于其低水溶性、副作用和多药耐药性，其临床应用受到限制。本研究旨在通过药物传递系统提高 VB 的治疗效果。为此，采用薄膜水化法制备了 PEG 化的长春碱囊泡（Pn-VB）并进行了理化性质表征。采用透析扩散法进行了药物释放模式研究。采用 MTT 法研究了 Pn-VB 对小鼠肺癌 TC-1 细胞的细胞毒性，并在荷肺癌 C57BL/6 小鼠中评价了其肿瘤抑制作用。囊泡的平均粒径、ζ 电位、包封率和载药量分别约为 234.3±11.4nm、-34.6±4.2mV、99.92±1.6%和 2.673±0.30%，而非 PEG 化囊泡的平均粒径和 ζ 电位分别约为 212.4nm 和-31.4mV。囊泡中药物的体外释放模式呈持续释放行为。与游离 VB 相比，Pn-VB 对 TC-1 细胞的毒性显著增加。在动物模型中，与游离 VB 相比，Pn-VB 表现出更强的肿瘤抑制作用和更长的生存时间。总之，与游离药物相比，Pn-VB 表现出适当的稳定性、高包封效率、较低的释放率和更强的对肺癌 TC-1 细胞的细胞毒性。因此，Pn-VB 可能是一种有前途的长春碱传递系统，可提高药物的生物利用度和治疗效果。
