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Phenylboronic Acid Functionalized Polycarbonate Hydrogels for Controlled Release of Polymyxin B in Pseudomonas Aeruginosa Infected Burn Wounds
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2018-03-06 , DOI: 10.1002/adhm.201701388
Sybil Obuobi 1 , Zhi Xiang Voo 2 , Mei W. Low 1 , Bertrand Czarny 1 , Vanitha Selvarajan 1 , Nor L. Ibrahim 2 , Yi Yan Yang 2 , Pui Lai Rachel Ee 1
Affiliation  

While physically crosslinked polycarbonate hydrogels are effective drug delivery platforms, their hydrophobic nature and lack of side chain functionality or affinity ligands for controlled release of hydrophilic drugs underscore the importance of their chemical compositions. This study evaluates an array of anionic hydrogel systems of phenylboronic acid functionalized triblock copolymers prepared via reversible physical interactions. Variation of key chemical functionalities while maintaining similar core structural features demonstrates the influence of the substitution position and protection of the boronic acid functionality on gel viscoelasticity and mechanical strength at physiological pH. The optimum gel systems obtained from the meta‐substituted copolymers (m‐PAP) are stable at physiological pH and nontoxic to mammalian dermal cells. The polymyxin B loaded m‐PAP hydrogels demonstrate controlled in vitro drug release kinetics and in vitro antimicrobial activity against Pseudomonas aeruginosa over 48 h. In vivo antimicrobial efficacy of the drug loaded hydrogels further corroborates the in vitro results, demonstrating sustained antimicrobial activity against P. aeruginosa burn wound infections. The current strategy described in this study demonstrates a straightforward approach in designing physiologically relevant boronic acid hydrogel systems for controlled release of cationic antimicrobials for future clinical applications.

中文翻译:

苯硼酸官能化聚碳酸酯水凝胶可控制铜绿假单胞菌感染烧伤伤口中多粘菌素B的释放

尽管物理交联的聚碳酸酯水凝胶是有效的药物递送平台,但它们的疏水性和对亲水性药物控制释放的侧链功能或亲和性配体的缺乏强调了其化学组成的重要性。这项研究评估通过可逆的物理相互作用制备的一系列由苯基硼酸官能化的三嵌段共聚物的阴离子水凝胶体系。在保持相似的核心结构特征的同时,关键化学功能的变化证明了取代位置和硼酸官能度的保护对生理pH下凝胶粘弹性和机械强度的影响。从meta获得的最佳凝胶系统预取代的共聚物(m-PAP)在生理pH值下稳定,对哺乳动物真皮细胞无毒。载有多粘菌素B的m-PAP水凝胶在48小时内显示出可控的体外药物释放动力学和体外对铜绿假单胞菌的抗菌活性。载有药物的水凝胶的体内抗菌功效进一步证实了体外结果,证明了针对铜绿假单胞菌烧伤创面感染的持续抗菌活性。这项研究中描述的当前策略展示了一种直接的方法,可用于设计生理相关的硼酸水凝胶系统,以控制阳离子抗菌剂的释放,以用于未来的临床应用。
更新日期:2018-03-06
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