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贻贝启发的可控药物释放水凝胶用于经皮给药:氢键和离子偶极相互作用。

Mussel-inspired controllable drug release hydrogel for transdermal drug delivery: Hydrogen bond and ion-dipole interactions.

机构信息

Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, 977 Gongyuan Road, Yanji 133002, China.

Department of Pharmaceutical Sciences, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.

出版信息

J Control Release. 2024 Jan;365:161-175. doi: 10.1016/j.jconrel.2023.11.016. Epub 2023 Nov 23.

Abstract

Hydrogels have broad application prospects in drug delivery due to their biocompatibility, high water content and three-dimensional structure. However, the regulation of drug release from hydrogels is an important issue in medical applications. At the same time, water also has an important impact on drug release. In this study, a hydrogel with hydrogen bond and ion dipole interaction (PAHDP) was prepared by introducing catechol group into polymer to regulate drug release. Ten model drugs were selected to explore the relationship and mechanism of action among polymer, drug and water. The results showed that PAHDP had excellent adhesion and safety. Drug release test showed that 10 kinds of drugs had different drug release trends, and the release amount was negatively correlated with drug polarizability and LogP. In addition, in vitro transdermal test and pharmacokinetic results showed that the hydrogel based on PAHDP achieved increased or decreased blood drug concentration, and the area under the concentration-time curve (AUC) of >1.5 times showed its potential to regulate drug release. The mechanism study showed that the hydrogen bond and ion dipole interaction between polymer and drug were affected by drug polarizability and LogP, and the distribution of water in different states was changed. Hydrogen bond and ion dipole interactions synergistically control drug release. Therefore, the mussel inspired PAHDP hydrogel has the potential to become a controllable drug delivery system.

摘要

水凝胶由于其生物相容性、高含水量和三维结构,在药物传递中有广泛的应用前景。然而,水凝胶中药物的释放调控是医学应用中的一个重要问题。同时,水对药物释放也有重要影响。在本研究中,通过在聚合物中引入儿茶酚基团,制备了具有氢键和离子偶极相互作用(PAHDP)的水凝胶,以调节药物释放。选择了 10 种模型药物来探索聚合物、药物和水之间的关系和作用机制。结果表明,PAHDP 具有优异的黏附性和安全性。药物释放试验表明,10 种药物具有不同的药物释放趋势,释放量与药物的极化率和 LogP 呈负相关。此外,体外透皮试验和药代动力学结果表明,基于 PAHDP 的水凝胶实现了增加或减少血液药物浓度,AUC 增加 1.5 倍以上表明其具有调节药物释放的潜力。机制研究表明,聚合物与药物之间的氢键和离子偶极相互作用受药物极化率和 LogP 的影响,改变了不同状态下的水分布。氢键和离子偶极相互作用协同控制药物释放。因此,贻贝类启发的 PAHDP 水凝胶具有成为可控药物传递系统的潜力。

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