Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, Madhya Pradesh, 470003, India.
Bhagyoday Tirth Pharmacy College, Sagar, Madhya Pradesh, India.
Drug Deliv Transl Res. 2015 Dec;5(6):596-610. doi: 10.1007/s13346-015-0255-x.
Cancer is the second leading cause of death worldwide, the deaths are projected to continue rising, with an estimated 12 million deaths in 2030. The aim of the present investigation is to prepare and compare the uncoated (U-CH NP) and eudragit S 100-coated (E-U-CH NP) chitosan nanoparticles encapsulating a caspase 3 activator (UCN 01), by ionic gelation method. The prepared formulations were studied for various parameters like particles size, zeta potential, transmission electron microscopy, atomic force microscopy, in vitro release study, ex vivo study using Caco 2 colon cancer cell line, and in vivo studies. The particle size and zeta potential of developed formulation was found to be particle size of 168 ± 3.7 nm and +35.8 ± 3.7 for U-CH NP and 265 ± 4.1 nm and +22.3 ± 1.1 for E-U-CH NP. TEM and AFM images revealed that U-CH NPs were round in shape and smoother at surface as compared to E-U-CH NP which have irregular surface due to coating. The E-U-CH NP showed better in vitro release than uncoated formulation in SCF (pH 6.8) than in SGF (pH 1.2). The cytotoxicity was performed by MTT assay. U-CH NP showed enhanced cytotoxicity as compared to blank (without drug) formulation. There was an increase in caspase 3 activity of U-CH NP as compared to UCN 01 alone. E-U-CH NP showed better tumor regression ability than U-CH NP. The results of plasma profile and tumor regression study demonstrated that E-U-CH NP has continuous release profile of UCN 01 and comprehensive residence time. Thus, it is better acceptable than free UCN 01 and may be a potential delivery system for the targeting and treatment of colon cancer.
癌症是全球第二大死亡原因，预计死亡人数将继续上升，到 2030 年预计将有 1200 万人死亡。本研究的目的是通过离子凝胶法制备并比较未涂层（U-CH NP）和 Eudragit S 100 涂层（E-U-CH NP）壳聚糖纳米粒包封 caspase 3 激活剂（UCN 01）。对制备的制剂进行了各种参数的研究，如粒径、Zeta 电位、透射电子显微镜、原子力显微镜、体外释放研究、用 Caco 2 结肠癌细胞系进行的离体研究和体内研究。发现开发制剂的粒径和 Zeta 电位分别为 U-CH NP 的 168±3.7nm 和+35.8±3.7，E-U-CH NP 的 265±4.1nm 和+22.3±1.1。TEM 和 AFM 图像显示，与表面不规则的 E-U-CH NP 相比，U-CH NP 呈圆形且表面更光滑。E-U-CH NP 在 SCF（pH 6.8）中的体外释放优于未涂层制剂，而在 SGF（pH 1.2）中则不如未涂层制剂。通过 MTT 测定法进行细胞毒性测定。与空白（无药物）制剂相比，U-CH NP 显示出增强的细胞毒性。与单独的 UCN 01 相比，U-CH NP 的 caspase 3 活性增加。E-U-CH NP 显示出比 U-CH NP 更好的肿瘤消退能力。血浆特征和肿瘤消退研究的结果表明，E-U-CH NP 具有 UCN 01 的持续释放特征和综合停留时间。因此，它比游离 UCN 01 更易被接受，可能是针对结肠癌的靶向治疗的潜在给药系统。
