纳米载体
生物相容性
药物输送
乙二醇
药品
前药
抗菌活性
化学
两亲性
席夫碱
组合化学
纳米技术
体内
控制释放
生物物理学
药理学
材料科学
细菌
生物化学
有机化学
立体化学
生物
生物技术
聚合物
遗传学
共聚物
作者
Dawei Li,Guoke Tang,Hui Yao,Yuqi Zhu,Changgui Shi,Qiang Fu,Fei Yang,Xing Wang
标识
DOI:10.1016/j.bioactmat.2022.02.018
摘要
In the current global crisis of antibiotic resistance, delivery systems are emerging to combat resistant bacteria in a more efficient manner. Despite the significant advances of antibiotic nanocarriers, many challenges like poor biocompatibility, premature drug release, suboptimal targeting to infection sites and short blood circulation time are still challenging. To achieve targeted drug delivery and enhance antibacterial activity, here we reported a kind of pH-responsive nanoparticles by simply self-assembly of an amphiphilic poly(ethylene glycol)-Schiff-vancomycin (PEG-Schiff-Van) prodrug and free Van in one drug delivery system. The acid-liable Schiff base furnished the PEG-Schiff-Van@Van with good storage stability in the neutral environment and susceptible disassembly in response to faintly acidic condition. Notably, on account of the combination of physical encapsulation and chemical conjugation of vancomycin, these nanocarriers with favorable biocompatibility and high drug loading capacity displayed a programmed drug release behavior, which was capable of rapidly reaching high drug concentration to effectively kill the bacteria at an early period and continuously exerting an bacteria-sensitive effect whenever needed over a long period. In addition, more Schiff-base moieties within the PEG-Schiff-Van@Van nanocarriers may also make great contributions on promoting the antimicrobial activity. Using this strategy, this system was designed to have programmable structural destabilization and sequential drug release due to changes in pH that were synonymous with bacterial infection sites, thereby presenting prominent antibacterial therapy both in vitro and in vivo. This work represents a synergistic strategy on offering important guidance to rational design of multifunctional antimicrobial vehicles, which would be a promising class of antimicrobial materials for potential clinical translation.
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