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苯并咪唑壳聚糖季铵盐载药纳米凝胶的抗氧化和抗肿瘤活性的改善。

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels.

机构信息

Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.

University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Mar Drugs. 2024 Jan 11;22(1):40. doi: 10.3390/md22010040.

DOI:10.3390/md22010040
PMID:38248665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10817266/
Abstract

The present study focused on the design and preparation of acid-responsive benzimidazole-chitosan quaternary ammonium salt (BIMIXHAC) nanogels for a controlled, slow-release of Doxorubicin HCl (DOX.HCl). The BIMIXHAC was crosslinked with sodium tripolyphosphate (TPP) using the ion crosslinking method. The method resulted in nanogels with low polydispersity index, small particle size, and positive zeta potential values, indicating the good stability of the nanogels. Compared to hydroxypropyl trimethyl ammonium chloride chitosan-Doxorubicin HCl-sodium tripolyphosphate (HACC-D-TPP) nanogel, the benzimidazole-chitosan quaternary ammonium salt-Doxorubicin HCl-sodium tripolyphosphate (BIMIXHAC-D-TPP) nanogel show higher drug encapsulation efficiency and loading capacity (BIMIXHAC-D-TPP 93.17 ± 0.27% and 31.17 ± 0.09%), with acid-responsive release profiles and accelerated release in vitro. The hydroxypropyl trimethyl ammonium chloride chitosan-sodium tripolyphosphate (HACC-TPP), and benzimidazole-chitosan quaternary ammonium salt-sodium tripolyphosphate (BIMIXHAC-TPP) nanogels demonstrated favorable antioxidant capability. The assay of cell viability, measured by the MTT assay, revealed that nanogels led to a significant reduction in the cell viability of two cancer cells: the human lung adenocarcinoma epithelial cell line (A549) and the human breast cancer cell line (MCF-7). Furthermore, the BIMIXHAC-D-TPP nanogel was 2.96 times less toxic than DOX.HCl to the mouse fibroblast cell line (L929). It was indicated that the BIMIXHAC-based nanogel with enhanced antioxidant and antitumor activities and acidic-responsive release could serve as a potential nanocarrier.

摘要

本研究专注于设计和制备酸响应性苯并咪唑壳聚糖季铵盐（BIMIXHAC）纳米凝胶，用于控制盐酸阿霉素（DOX.HCl）的缓慢释放。BIMIXHAC 与三聚磷酸钠（TPP）通过离子交联法交联。该方法得到的纳米凝胶具有低多分散指数、小粒径和正 ζ 电位值，表明纳米凝胶具有良好的稳定性。与羟丙基三甲基氯化铵壳聚糖-盐酸阿霉素-三聚磷酸钠（HACC-D-TPP）纳米凝胶相比，苯并咪唑壳聚糖季铵盐-盐酸阿霉素-三聚磷酸钠（BIMIXHAC-D-TPP）纳米凝胶具有更高的药物包封效率和载药量（BIMIXHAC-D-TPP 为 93.17 ± 0.27%和 31.17 ± 0.09%），具有酸响应释放特性和体外加速释放。羟丙基三甲基氯化铵壳聚糖-三聚磷酸钠（HACC-TPP）和苯并咪唑壳聚糖季铵盐-三聚磷酸钠（BIMIXHAC-TPP）纳米凝胶表现出良好的抗氧化能力。通过 MTT 测定法测定的细胞活力测定表明，纳米凝胶导致两种癌细胞（人肺腺癌细胞系（A549）和人乳腺癌细胞系（MCF-7））的细胞活力显著降低。此外，与 DOX.HCl 相比，BIMIXHAC-D-TPP 纳米凝胶对小鼠成纤维细胞系（L929）的毒性降低了 2.96 倍。结果表明，具有增强的抗氧化和抗肿瘤活性以及酸响应性释放的基于 BIMIXHAC 的纳米凝胶可以作为一种潜在的纳米载体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/fc0a207650c0/marinedrugs-22-00040-sch002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/fc0a207650c0/marinedrugs-22-00040-sch002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/4475e549a76d/marinedrugs-22-00040-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/7f04c1c2e900/marinedrugs-22-00040-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/e95d74fb15a9/marinedrugs-22-00040-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/cf65dbcff41f/marinedrugs-22-00040-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/05e91aa220e7/marinedrugs-22-00040-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/4a18b5c39e68/marinedrugs-22-00040-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/060f31d3165e/marinedrugs-22-00040-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dc8/10817266/fc0a207650c0/marinedrugs-22-00040-sch002.jpg

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