Department of Chemistry, Razi University, Kermanshah, Iran.
Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
AAPS PharmSciTech. 2019 Jul 22;20(7):259. doi: 10.1208/s12249-019-1466-0.
The local delivery of chemotherapy drugs using implantable drug delivery systems is a promising strategy to the treatment of malignant brain tumors. In this study, core/shell chitosan-poly ethylene oxide-carbon quantum dots/carboxymethyl cellulose-polyvinyl alcohol (CS-PEO-CQDs/CMC-PVA) nanofibers were successfully prepared through coaxial electrospinning as a biodegradable polymeric implant for the local delivery of temozolomide (TMZ). Fluorescent carbon dots with carboxyl-rich surface were used as a trackable drug delivery agent for the localized cancer treatment. The effects of several preparation parameters such as voltage, shell to core flow rate, CS/PEO ratio, and PVA/CMC ratio on the structure of nanofibers were investigated. The best nanofibers were obtained in the condition of CS/PEO ratio of 80:20, CMC/PVA ratio of 20:80, shell to core flow rate of 3, and voltage of 25 V. SEM images showed that such nanofibers possess a smooth surface and bead-less structures. The results obtained by DSC indicated that TMZ trapped in the nanofibers existed in an amorphous or disordered crystalline status. In vitro release profile of TMZ from core-shell nanofibers had biphasic patterns. After an initial burst, a continuous drug release was observed for up to 28 days. The in vitro antitumor activity of CQDs-TMZ was tested against the tumor U251 cell lines than the free drug. It has been found that the cytotoxicity of TMZ to U251 cancer cells is enhanced when TMZ is conjugated with CQDs.
局部递送化疗药物的植入式药物输送系统是治疗恶性脑肿瘤的一种很有前途的策略。在这项研究中，通过同轴静电纺丝成功制备了壳聚糖-聚环氧乙烷-碳量子点/羧甲基纤维素-聚乙烯醇（CS-PEO-CQDs/CMC-PVA）核壳纳米纤维作为一种可生物降解的聚合物植入物，用于局部递送替莫唑胺（TMZ）。具有丰富羧基表面的荧光碳点被用作局部癌症治疗的可追踪药物输送剂。研究了几种制备参数（如电压、壳核流速比、CS/PEO 比和 PVA/CMC 比）对纳米纤维结构的影响。在 CS/PEO 比为 80:20、CMC/PVA 比为 20:80、壳核流速比为 3 和电压为 25 V 的条件下，得到了最佳的纳米纤维。SEM 图像表明，这些纳米纤维具有光滑的表面和无珠状结构。DSC 结果表明，包埋在纳米纤维中的 TMZ 以无定形或无序结晶状态存在。TMZ 从核壳纳米纤维中的体外释放曲线呈两相模式。在初始突释后，观察到长达 28 天的持续药物释放。CQDs-TMZ 的体外抗肿瘤活性通过 U251 肿瘤细胞系进行了测试，结果优于游离药物。研究发现，当 TMZ 与 CQDs 偶联时，TMZ 对 U251 癌细胞的细胞毒性增强。
