Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema.
Chiral Supramolecular Hydrogel Enhanced Transdermal Delivery of Sodium Aescinate to Modulate M1 Macrophage Polarization Against Lymphedema.
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DOI：
10.1002/advs.202303495
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发表时间：
2024-02
期刊：
影响因子：
15.1
通讯作者：
Feng, Chuanliang
中科院分区：
文献类型：
--
作者：
Wang, Xueqian;Cui, Chunxiao;Meng, Xinxian;Han, Chengyao;Wu, Beibei;Dou, Xiaoqiu;Zhao, Changli;Zhang, Yixin;Li, Ke;Feng, Chuanliang
七叶皂苷钠（SA）由于能够调节M1巨噬细胞中细胞因子的表达而显示出巨大的治疗水肿的潜力，然而，在临床实践中，它通常是静脉内给药的，并且常常伴随严重的毒副作用和短的代谢周期。本文制备了SA-负载手性超分子水凝胶，以证明SA对水肿的治疗作用，并提高其安全性和透皮效率。体外研究表明，SA负载的手性超分子水凝胶可以通过抑制M1巨噬细胞极化来调节局部免疫反应。通常，由于手性胶凝剂和角质层之间的高对映体选择性，这些手性水凝胶可以显著增加SA的渗透性，具有良好的生物相容性，并且发现L型水凝胶具有优于D型水凝胶的药物渗透性。体内研究表明，通过手性水凝胶局部递送SA导致对水肿的显著治疗效果。具体而言，它可以下调炎性细胞因子的水平，减少纤维化的发展，促进淋巴管的再生。本研究开始使用SA治疗水肿，并创建一个有效的手性生物平台，以改善局部给药。说明主要皮肤结构（表皮、真皮和皮下组织）和药物分子的渗透机制。这些手性水凝胶可以显著增加SA（七叶皂苷钠）的渗透性，由于手性胶凝剂和角质层（皮肤的主要屏障）之间的高对映体选择性，具有良好的生物相容性。这些SA负载的手性超分子水凝胶可以通过抑制M1巨噬细胞极化来调节局部免疫反应，以减轻水肿。
Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA‐loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA‐ loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L‐type hydrogels are found to have preferable drug penetration over D‐type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration. Illustration of the major skin structure (epidermis, dermis, and subcutaneous tissue) and the penetration mechanism of drug molecules. These chiral hydrogels can significantly increase the permeability of SA (sodium aescinate) with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum (the main barrier of skin). And these SA‐loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization to relieve lymphedema.
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