Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
J Control Release. 2017 Feb 10;247:145-152. doi: 10.1016/j.jconrel.2017.01.003. Epub 2017 Jan 7.
Aminoglycosides are a family of critically important antibiotics for the treatment of serious infections including multidrug-resistant pathogens. However, clinical use of aminoglycoside antibiotics is compromised by bacterial biofilm formation at subinhibitory concentrations or adverse side effects such as ototoxicity and nephrotoxicity at high antibiotic doses. Preparation of aminoglycoside formulation that allows on-demand drug delivery is a solution to this sticky issue. Here, we designed a new type of aminoglycoside hydrogels by cross-linking oxidized polysaccharides such as dextran, carboxymethyl cellulose, alginate, and chondroitin using aminoglycosides as cross-linkers. The hydrogel modulus, degradation rate and release kinetics can be precisely modulated by tailoring the aminoglycoside dose during gel formation. The aminoglycoside hydrogel showed fast gelation, self-healing and on-demand drug release behaviors, and high antibacterial activities in vitro and in vivo against both Gram-positive and Gram-negative bacteria. This study provides a facile and promising strategy to develop smart hydrogels for topical administration of aminoglycoside antibiotics.
氨基糖苷类抗生素是一类重要的抗生素，可用于治疗严重感染，包括多药耐药病原体。然而，氨基糖苷类抗生素的临床应用受到细菌在亚抑菌浓度下形成生物膜以及高抗生素剂量下产生耳毒性和肾毒性等不良反应的影响。制备能够按需给药的氨基糖苷类药物制剂是解决这一难题的方法。在这里，我们通过使用氨基糖苷类作为交联剂交联氧化多糖（如葡聚糖、羧甲基纤维素、海藻酸钠和硫酸软骨素）来设计新型氨基糖苷类水凝胶。通过在凝胶形成过程中调整氨基糖苷类药物的剂量，可以精确调节水凝胶的模量、降解率和释放动力学。氨基糖苷类水凝胶表现出快速的凝胶化、自修复和按需药物释放行为，以及体外和体内对革兰氏阳性菌和革兰氏阴性菌的高抗菌活性。这项研究为开发用于局部给予氨基糖苷类抗生素的智能水凝胶提供了一种简单而有前景的策略。
