具有分步响应释放策略的10-羟基喜树碱负载的以淀粉为基础的微胶囊,以实现靶向控制释放。
10-hydroxycamptothecin-loaded starch-based microcapsules with the stepwise responsive release strategy for targeted controlled release.
发表日期:2023 Aug 20
作者:
Qingye Meng, Shuangling Zhong, Jia Wang, Yan Gao, Xuejun Cui
来源:
Cellular & Molecular Immunology
摘要:
对药物在靶标位置的控制和准确释放一直是研究的重点。尤其在癌症治疗方面,经济、方便和准确的传递策略有助于减少药物对正常组织的毒副作用,提高药物的有效性。本研究通过基于硫化改性淀粉的声化学法制备了谷胱甘肽(GSH)响应微囊(FA-RSMCs)。10-羟基喜树碱(HCPT)被设计为响应活性氧(ROS)的聚型前药(polyHCPT),被加载到微囊的核心部分以获得逐步释放的药物传递载体。在肿瘤微环境中,FA-RSMCs首先通过GSH响应切割释放polyHCPT,然后通过ROS响应切割释放完整的HCPT药物分子。在模拟肿瘤微环境中的实验结果表明,FA-RSMCs在体外表现出良好的级联响应释放特性。它在体外展现了良好的抗肿瘤能力和对正常细胞的保护作用。这种策略提高了通过微囊实现HCPT的靶向递送的准确性和安全性,具有临床应用的潜力。版权所有 © 2023. Elsevier B.V. 发布。
Controlled and accurate drug release at the target site have been the focus of research. Especially in cancer therapy, economical, convenient and accurate delivery strategies could help to reduce the toxic effects of drugs on normal tissues and improve drug availability. In the study, glutathione (GSH)-responsive microcapsules (FA-RSMCs) were prepared by sonochemical method based on thiolated modified starch. 10-Hydroxycamptothecin (HCPT) was designed as a reactive oxygen species (ROS)-responsive polyprodrug (polyHCPT), which was loaded into the core of the microcapsules to obtain stepwise released drug delivery carriers. In the tumor microenvironment, FA-RSMCs first triggered GSH-responsive cleavage to release polyHCPT, followed by ROS-responsive cleavage of polyHCPT to release intact HCPT drug molecules. The results of experiments in simulated tumor microenvironment showed that FA-RSMCs exhibited good cascade-response release properties in vitro. It exhibited good anti-tumor ability and protection of normal cells in cytotoxicity in vitro. This strategy enhanced the accuracy and safety of targeted delivery of HCPT via microcapsules, which has potential for clinical application.Copyright © 2023. Published by Elsevier B.V.