School of Physical Science and Technology, ShanghaiTech University, 393 Huaxia Middle Rd., Pudong, Shanghai 201210, China.
Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
ACS Appl Mater Interfaces. 2024 Oct 2;16(39):51981-51993. doi: 10.1021/acsami.4c09185. Epub 2024 Sep 18.
is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to . In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against is as low as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating infection.
幽门螺杆菌是导致胃腺癌的主要原因，它困扰着全球一半以上的人口，严重影响着人类的健康。然而，由于胃部恶劣的微环境、短的药物滞留时间和生理屏障，通过有效的药物输送和口服生物利用度来实现对 感染的有效治疗仍然是一个挑战。此外， 已经对许多临床抗生素表现出耐药性。抗菌肽 (AMPs) 对 表现出显著的治疗效果，而不易产生耐药性，这表明它们在治疗与 相关的疾病方面具有潜在的应用价值。在本文中，我们报告了一种具有 pH 响应性和受控肽释放特性的 AMP（GE33）水凝胶的设计和合成，其中 AMP 对 的最小抑菌浓度低至 1 μg/mL。在中性 pH 条件下，GE33 自组装成稳定的肽水凝胶，但在酸性条件下会分解成单体或低聚物。当水凝胶经口服给药时，酸性胃环境会促进活性 AMP 分子从水凝胶中快速释放，并立即靶向胃壁中的 。此外，剩余的肽被水凝胶保护，从而延长其在胃中的滞留时间，实现持续的药物释放。活性分子 GE33 的这种受控和持续释放方式提高了药物的生物利用度，同时具有出色的杀菌效果，为治疗 感染开辟了巨大的潜力。
