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利用温敏水凝胶基药物库实现近红外光控按需抗生素释放,用于对抗细菌感染。

Near-infrared light-controllable on-demand antibiotics release using thermo-sensitive hydrogel-based drug reservoir for combating bacterial infection.

机构信息

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, PR China.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou Road, Nanjing 210096, PR China.

出版信息

Biomaterials. 2019 Jan;188:83-95. doi: 10.1016/j.biomaterials.2018.09.045. Epub 2018 Oct 2.

Abstract

A near-infrared (NIR) light-triggerable thermo-sensitive hydrogel-based drug reservoir that can realize on-demand antibiotics release and hyperthermia-assisted bacterial inactivation was prepared to combat bacterial infection and promote wound healing. The drug reservoir was fabricated by mixing ciprofloxacin (Cip, a potent antibiotic)-loaded polydopamine (PDA) nanoparticles (NPs) and glycol chitosan (GC) to form an injectable hydrogel (PDA NP-Cip/GC hydrogel, abbreviated as Gel-Cip). On the one hand, the positive charge of GC and the adsorbability of PDA NPs made bacteria be readily trapped on the surface of Gel-Cip. On the other hand, the Gel-Cip exhibited minimal leakage under physiological conditions, but could boost Cip release upon NIR light irradiation. Meanwhile, NIR light irradiation could activate the photothermal PDA NPs, and the generated local hyperthermia induced the destruction of the bacterial integrity, leading to bacterial inactivation in a synergistic way. Moreover, the exceptional bacterial killing activity and outstanding wound healing ability of the system were also verified by the S. aureus-infected mouse skin defect model. Taken together, the light-activatable hydrogel-based platform allows us to release antibiotics more precisely, eliminate bacteria more effectively, and inhibit bacteria-induced infections more persistently, which will advance the development of novel antibacterial agents and strategies.

摘要

一种近红外(NIR)光触发的温敏水凝胶药物库,能够实现按需释放抗生素和热疗辅助细菌失活,以对抗细菌感染和促进伤口愈合。该药物库是通过混合载有环丙沙星(Cip,一种强效抗生素)的聚多巴胺(PDA)纳米粒子(NPs)和壳聚糖(GC)来制备可注射水凝胶(PDA NP-Cip/GC 水凝胶,简称 Gel-Cip)。一方面,GC 的正电荷和 PDA NPs 的吸附性使细菌很容易被困在 Gel-Cip 的表面。另一方面,Gel-Cip 在生理条件下几乎没有泄漏,但在近红外光照射下能促进 Cip 的释放。同时,近红外光照射可以激活光热 PDA NPs,产生的局部热疗导致细菌完整性被破坏,从而协同实现细菌失活。此外,金黄色葡萄球菌感染的小鼠皮肤缺损模型也验证了该系统的出色的杀菌活性和优异的伤口愈合能力。总之,基于光激活水凝胶的平台可以更精确地释放抗生素,更有效地消除细菌,并更持久地抑制细菌引起的感染,这将推动新型抗菌剂和策略的发展。

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