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用于肝癌的生物响应性壳聚糖-聚(L-乳酸)复合纳米凝胶

Bio-responsive chitin-poly(L-lactic acid) composite nanogels for liver cancer.

机构信息

Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.

Amrita Centre for Nanosciences and Molecular Medicine, Amrita Institute of Medical Sciences and Research Centre, Amrita Vishwa Vidyapeetham University, Kochi 682041, India.

出版信息

Colloids Surf B Biointerfaces. 2014 Jan 1;113:394-402. doi: 10.1016/j.colsurfb.2013.09.023. Epub 2013 Sep 20.

Abstract

Hepatic carcinoma (HCC) is one of the most common cancer and its treatment has been considered a therapeutic challenge. Doxorubicin (Dox) is one of the most important chemotherapeutic agents used in the treatment for liver cancer. However, the efficacy of Dox therapy is restricted by the dose-dependent toxic side effects. To overcome the cardiotoxicity of Dox as well as the current problems of conventional modality treatment of HCC, we developed a locally injectable, biodegradable, and pH sensitive composite nanogels for site specific delivery. Both control and Dox loaded composite nanogel systems were analyzed by DLS, SEM, FTIR and TG/DTA. The size ranges of the control composite nanogels and their drug loaded counterparts were found to be 90±20 and 270±20 nm, respectively. The control chitin-PLA CNGs and Dox-chitin-PLA CNGs showed higher swelling and degradation in acidic pH. Drug entrapment efficiency and in vitro drug release studies were carried out and showed a higher drug release at acidic pH compared to neutral pH. Cellular internalization of the nanogel systems was confirmed by fluorescent microscopy. The cytotoxicity of the composite nanogels was analyzed toward HepG2 (human liver cancer) cell lines. Furthermore, the results of in vitro hemolytic assay and coagulation assay substantiate the blood compatibility of the system. Overall Dox-chitin-PLA CNGs system could be a promising anticancer drug delivery system for liver cancer therapy.

摘要

肝细胞癌(HCC)是最常见的癌症之一,其治疗一直被认为是一个治疗挑战。阿霉素(Dox)是治疗肝癌中使用的最重要的化疗药物之一。然而,Dox 治疗的疗效受到剂量依赖性毒副作用的限制。为了克服 Dox 的心脏毒性以及 HCC 传统治疗模式的当前问题,我们开发了一种局部可注射、可生物降解和 pH 敏感的复合纳米凝胶,用于靶向递药。通过 DLS、SEM、FTIR 和 TG/DTA 分析了对照和载 Dox 的复合纳米凝胶系统。发现对照复合纳米凝胶及其载药对应物的粒径范围分别为 90±20nm 和 270±20nm。在酸性 pH 下,对照壳聚糖-PLA CNG 和 Dox-壳聚糖-PLA CNG 的溶胀和降解更高。进行了药物包封效率和体外药物释放研究,结果表明在酸性 pH 下与中性 pH 相比,药物释放更高。通过荧光显微镜证实了纳米凝胶系统的细胞内化。分析了复合纳米凝胶对 HepG2(人肝癌)细胞系的细胞毒性。此外,体外溶血和凝血测定的结果证实了该系统的血液相容性。总之,Dox-壳聚糖-PLA CNG 系统可能是治疗肝癌的有前途的抗癌药物递送系统。

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