Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Punjab, Pakistan.
Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Punjab, Pakistan.
Life Sci. 2021 Feb 15;267:118971. doi: 10.1016/j.lfs.2020.118971. Epub 2020 Dec 29.
The study aimed to develop, characterize, and evaluate poly (ɛ-caprolactone) (PCL) based nanoparticles for the sustained release behaviour of cytarabine and to investigate the in vitro anti-cancer influence on KG-1 leukemic cell line.
Nanoprecipitation method was used for the preparation of cytarabine loaded PCL nanoparticles. The developed nanoparticles were characterized for physicochemical properties and the anti-leukemic effect on the KG-1 cell line was evaluated.
A total number of five formulations were prepared with size range from 120.5 ± 1.18 to 341.5 ± 3.02, entrapment efficiency (41.31 ± 0.49 to 62.28 ± 0.39%), spherical morphology, negative zeta potentials, considerable particle size distribution, compatibility between the drug and excipients and thermal stability. X-ray diffraction analysis confirmed the successful incorporation of cytarabine in PCL polymer. In vitro drug release in phosphate buffer saline (pH 7.4) showed initial burst release followed by sustained release up to 48 h. The sustained release behaviour efficiently increased the toxicity of cytarabine-loaded PCL nanoparticles to KG-1 (leukemic) and MCF-7 (breast cancer) cell lines in time dependent manner with lower IC values than that of drug solution. The flow cytometry study revealed the better apoptotic activity of cytarabine loaded PCL nanoparticle against treated KG-1 cell line. The western blot analysis confirmed the upregulation of cleaved caspase-3 and downregulation of Bcl-2 protein.
The experimental results suggest that cytarabine loaded PCL nanoparticles is an efficient carrier to prevent the dose associated toxicity while providing sustained release pattern to ensure maximum anti-cancer influence.
本研究旨在开发、表征和评估基于聚（ε-己内酯）（PCL）的纳米粒，以实现阿糖胞苷的持续释放行为，并研究其对 KG-1 白血病细胞系的体外抗癌影响。
采用纳米沉淀法制备载阿糖胞苷的 PCL 纳米粒。对所开发的纳米粒进行理化性质表征，并评价其对 KG-1 细胞系的抗白血病作用。
共制备了 5 种制剂，粒径范围为 120.5±1.18 至 341.5±3.02，包封效率为 41.31±0.49 至 62.28±0.39%，呈球形形态，具有负的 Zeta 电位，颗粒分布均匀，药物与辅料相容性好，热稳定性好。X 射线衍射分析证实阿糖胞苷成功掺入 PCL 聚合物中。在磷酸盐缓冲盐水（pH 7.4）中的体外药物释放显示初始突释后持续释放至 48 小时。持续释放行为有效地增加了载阿糖胞苷的 PCL 纳米粒对 KG-1（白血病）和 MCF-7（乳腺癌）细胞系的毒性，其 IC50 值低于药物溶液。流式细胞术研究表明，载阿糖胞苷的 PCL 纳米粒对处理后的 KG-1 细胞系具有更好的凋亡活性。Western blot 分析证实 cleaved caspase-3 上调和 Bcl-2 蛋白下调。
实验结果表明，载阿糖胞苷的 PCL 纳米粒是一种有效的载体，可防止与剂量相关的毒性，同时提供持续释放模式，以确保最大的抗癌效果。
