Hyaluronic acid-based hydrogels containing covalently integrated drug depots: implication for controlling inflammation in mechanically stressed tissues.
Hyaluronic acid-based hydrogels containing covalently integrated drug depots: implication for controlling inflammation in mechanically stressed tissues.
复制标题
含有共价整合药物库的基于透明质酸的水凝胶：对于控制机械应力组织中的炎症的意义。
DOI：
10.1021/bm4011276
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发表时间：
2013
影响因子：
6.2
通讯作者：
Jia,Xinqiao
中科院分区：
文献类型：
--
作者：
Xiao,Longxi;Tong,Zhixiang;Chen,Yingchao;Pochan,DarrinJ;Sabanayagam,ChandranR;Jia,Xinqiao
含有共价整合的软且可变形药物库的合成水凝胶能够响应机械力释放治疗分子，是治疗通常承受负荷的退化组织的有吸引力的候选者。在此，可自由基交联的嵌段共聚物胶束（xBCM）由两亲性嵌段共聚物（由丙烯酸2-羟乙酯部分改性的亲水性聚（丙烯酸）（PAA）和疏水性聚（丙烯酸正丁酯）（PnBA）组成）组装而成，用作药物库和微观交联剂，用于制备基于透明质酸（HA）的水凝胶。含有共价整合胶束 (HAxBCM) 的 HA 水凝胶是通过甲基丙烯酸缩水甘油酯 (GMA) 修饰的 HA (HAGMA) 在 xBCM 存在下进行自由基聚合制备的。当使用由不含任何可聚合双键的母体PAA-b-PnBA制备的胶束时，获得了含有物理捕获的胶束(HApBCM)的水凝胶。在 HAGMA 前体溶液中添加 xBCM 加速了凝胶化动力学并改变了水凝胶的机械性能。所得 HAxBCM 凝胶的弹性模量为 847 ± 43 Pa，压缩模量为 9.2 ± 0.7 kPa。采用荧光相关光谱法对尼罗红 (NR) 标记的 xBCM 进行扩散分析，证实了 xBCM 在 HA 网络中的共价固定。 HA 凝胶中负载地塞米松 (DEX) 的 xBCM 的共价整合显着减少了初始突释，并提供了长时间的持续释放。重要的是，通过以应变依赖性方式间歇施加外部压缩，加速了 HAxBCM 凝胶中 DEX 的释放。在释放 DEX 的 HAxBCM 凝胶存在下培养巨噬细胞可显着减少炎症细胞因子的细胞产生。在合成基质中结合机械响应模块提供了一种新的策略来收集愈合伤口中存在的机械应力以启动组织修复。
Synthetic hydrogels containing covalently integrated soft and deformable drug depots capable of releasing therapeutic molecules in response to mechanical forces are attractive candidates for the treatment of degenerated tissues that are normally load bearing. Herein, radically cross-linkable block copolymer micelles (xBCM) assembled from an amphiphilic block copolymer consisting of hydrophilic poly(acrylic acid) (PAA) partially modified with 2-hydroxyethyl acrylate, and hydrophobic poly(n-butyl acryclate) (PnBA) were employed as the drug depots and the microscopic cross-linkers for the preparation of hyaluronic acid (HA)-based, hydrogels. HA hydrogels containing covalently integrated micelles (HAxBCM) were prepared by radical polymerization of glycidyl methacrylate (GMA)-modified HA (HAGMA) in the presence ofxBCMs. When micelles prepared from the parent PAA-b-PnBA without any polymerizable double bonds were used, hydrogels containing physically entrapped micelles (HApBCM) were obtained. The addition ofxBCMs to a HAGMA precursor solution accelerated the gelation kinetics and altered the hydrogel mechanical properties. The resultant HAxBCM gels exhibit an elastic modulus of 847 ± 43 Pa and a compressive modulus of 9.2 ± 0.7 kPa. Diffusion analysis of Nile Red (NR)-labeledxBCMs employing fluorescence correlation spectroscopy confirmed the covalent immobilization ofxBCMs in HA networks. Covalent integration of dexamethasone (DEX)-loadedxBCMs in HA gels significantly reduced the initial burst release and provided sustained release over a prolonged period. Importantly, DEX release from HAxBCM gels was accelerated by intermittently applied external compression in a strain-dependent manner. Culturing macrophages in the presence of DEX-releasing HAxBCM gels significantly reduced cellular production of inflammatory cytokines. Incorporating mechano-responsive modules in synthetic matrices offers a novel strategy to harvest mechanical stress present in the healing wounds to initiate tissue repair.