Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences , East China Normal University , Shanghai 200241 , P. R. China.
Department of Orthopedic Oncology, Changzheng Hospital , The Second Military Medical University , Shanghai 200003 , P. R. China.
ACS Appl Mater Interfaces. 2018 May 2;10(17):15163-15173. doi: 10.1021/acsami.8b02527. Epub 2018 Apr 23.
Local bacterial infection is a challenging task and still remains a serious threat to human health in clinics. Systemic administration of antibiotics has only short-term antibacterial activity and usually causes adverse effects and bacterial resistance. A bioadhesive hydrogel with broad-spectrum and on-demand antibiotic activity is highly desirable. Here, we designed a pH-responsive nanocomposite hydrogel via a Schiff base linkage between oxidized polysaccharides and cationic dendrimers encapsulated with silver nanoparticles. The antibacterial components, both the cationic dendrimers and silver species, could be released in response to the acidity generated by growing bacteria. The released cationic polymer and silver exhibited a synergistic effect in antibacterial activity, and thus, the nanocomposite hydrogel showed potent antibacterial activity against both Gram-negative ( Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria ( Staphylococcus epidermidis and Staphylococcus aureus). The gel showed superior in vivo antibacterial efficacy against S. aureus infection compared with a commercial silver hydrogel at the same silver concentration. In addition, no obvious hemolytic toxicity, cytotoxicity, and tissue and biochemical toxicity were observed for the antibacterial hydrogel after incubation with cells or implantation. This study provides a facile and promising strategy to develop smart hydrogels to treat local bacterial infections.
局部细菌感染是一个具有挑战性的问题，在临床实践中仍然对人类健康构成严重威胁。全身性给予抗生素仅具有短期的抗菌活性，并且通常会引起不良反应和细菌耐药性。因此，人们迫切需要一种具有广谱和按需抗菌活性的生物黏附水凝胶。在这里，我们设计了一种通过氧化多糖与包裹银纳米粒子的阳离子树状大分子之间的席夫碱键合形成的 pH 响应性纳米复合水凝胶。抗菌成分（阳离子聚合物和银物种）可以响应细菌生长产生的酸度而释放。释放出的阳离子聚合物和银在抗菌活性方面表现出协同作用，因此，纳米复合水凝胶对革兰氏阴性（大肠杆菌和铜绿假单胞菌）和革兰氏阳性菌（表皮葡萄球菌和金黄色葡萄球菌）均表现出很强的抗菌活性。与相同银浓度的商业银水凝胶相比，该凝胶在治疗金黄色葡萄球菌感染方面表现出更好的体内抗菌功效。此外，在与细胞孵育或植入后，抗菌水凝胶没有表现出明显的溶血毒性、细胞毒性以及组织和生化毒性。本研究为开发用于治疗局部细菌感染的智能水凝胶提供了一种简单而有前景的策略。
