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可生物降解的二硫键交联壳聚糖/硬脂酸纳米粒用于结直肠癌细胞的双重药物递送。

Biodegradable disulfide crosslinked chitosan/stearic acid nanoparticles for dual drug delivery for colorectal cancer.

机构信息

School of Chemical Sciences and Advanced Materials Research Centre, Indian Institute of Technology Mandi, 175075, India.

Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.

出版信息

Carbohydr Polym. 2022 Oct 15;294:119833. doi: 10.1016/j.carbpol.2022.119833. Epub 2022 Jul 7.

DOI:10.1016/j.carbpol.2022.119833
PMID:35868778
Abstract

Herein, redox responsive chitosan/stearic acid nanoparticles (CSSA NPs) (≈200 nm) are developed for dual drug delivery. These degradable nanoparticles are prepared based on disulfide (SS) crosslinking chemistry avoiding the use of any external crosslinking agent. CSSA NPs are further loaded with both DOX (hydrophilic) and curcumin (hydrophobic) drugs with ≈86 % and ≈82 % encapsulation efficiency respectively. This approach of combining anticancer therapeutics having different mode of anticancer action allows to develop systems for cancer therapy with enhanced efficacy. In vitro drug release experiments clearly exhibit the low leakage of drug under physiological conditions while ≈98 % DOX and ≈96 % curcumin is released after 136 h under GSH reducing conditions. The cytotoxicity experiments against HCT116 cells demonstrate higher cytotoxicity of dual drug loaded CSSA NPs. In vivo biodistribution experiments with c57bl/6j mice confirms the retention of CSSA NPs in the colon area up to 24 h exhibiting their potential for colorectal cancer therapy.

摘要

本文开发了一种具有氧化还原响应性的壳聚糖/硬脂酸纳米粒子(CSSA NPs)(约 200nm),用于双重药物传递。这些可降解的纳米粒子是基于二硫键(SS)交联化学制备的,避免了使用任何外部交联剂。CSSA NPs 进一步负载亲水的 DOX 和疏水性的姜黄素,包封效率分别约为 86%和 82%。这种结合具有不同抗癌作用模式的抗癌治疗方法的方法允许开发具有增强疗效的癌症治疗系统。体外药物释放实验清楚地表明,在生理条件下药物泄漏低,而在 GSH 还原条件下 136 小时后,约 98%的 DOX 和 96%的姜黄素释放。对 HCT116 细胞的细胞毒性实验表明,双载药 CSSA NPs 具有更高的细胞毒性。用 c57bl/6j 小鼠进行的体内生物分布实验证实,CSSA NPs 可在结肠区域保留长达 24 小时,显示其在结直肠癌治疗中的潜力。

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