Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
Departamento de Ingeniería Química, Campus de "El Carmen", Universidad de Huelva, 21071 Huelva, Spain; Pro2TecS-Chemical Process and Product Technology Research Center, Universidad de Huelva, 21071 Huelva, Spain.
Int J Biol Macromol. 2020 Dec 15;165(Pt B):2205-2218. doi: 10.1016/j.ijbiomac.2020.10.006. Epub 2020 Oct 12.
This study investigates the impact of dual ionic and covalent cross-links (ion-XrL and cov-XrL) on the properties of chitosan-based (CTS) hydrogels as eco-friendly drug delivery systems (DDS) for the model drug diclofenac sodium (DCNa). Citric acid and a diiodo-trehalose derivative (ITrh) were the chosen ionic and covalent cross-linker, respectively. The novel hydrogels completely disintegrated within 96 h by means of a hydrolysis process mediated by the enzyme trehalase. As far as the authors are aware, this is the first time that a trehalose derivative has been used as a covalent cross-linker in the formation of biodegradable hydrogels. The impact of CTS concentration and degree of cov-XrL on rheological parameters were examined by means of an experimental model design and marked differences were found between the materials. Hydrogels with maximum elastic properties were achieved at high CTS concentrations and high degrees of cov-XrL. DCNa-loaded formulations displayed well-controlled drug-release profiles strongly dependent on formulation composition (from 17% to 40% in 72 h). Surprisingly, higher degrees of covalent cross-linking led to a boost in drug release. The formulations presented herein provides a simple and straightforward pathway to design fully biodegradable, tailor-made controlled drug delivery systems with improved rheological properties.
本研究考察了双重离子和共价交联（ion-XrL 和 cov-XrL）对壳聚糖基（CTS）水凝胶作为环保型药物输送系统（DDS）用于模型药物双氯芬酸钠（DCNa）的性能的影响。柠檬酸和二碘海藻糖衍生物（ITrh）分别作为离子和共价交联剂。新型水凝胶通过海藻糖酶介导的水解过程在 96 小时内完全分解。据作者所知，这是首次将海藻糖衍生物用作形成可生物降解水凝胶的共价交联剂。通过实验模型设计研究了 CTS 浓度和 cov-XrL 程度对流变学参数的影响，发现材料之间存在明显差异。在高 CTS 浓度和高 cov-XrL 程度下，水凝胶达到最大弹性性能。载有 DCNa 的制剂显示出良好的药物释放曲线，强烈依赖于制剂组成（72 小时内从 17%到 40%）。令人惊讶的是，更高程度的共价交联导致药物释放增加。本文提供了一种简单直接的方法来设计完全可生物降解的、定制的、具有改善流变学性能的控释药物输送系统。
