{"title":"一种含有抗生素的多功能水凝胶敷料,用于感染伤口的愈合。","authors":"","doi":"10.1016/j.ijpharm.2024.124770","DOIUrl":null,"url":null,"abstract":"<div><div>Wound bacterial infections can significantly delay the healing process and even lead to fetal sepsis. There is a need for multifunctional dressings that possess antibacterial property, tissue adhesive property, self-healing capability, and biocompatibility to effectively treat bacteria-infected wound. In this study, we report a dual dynamically crosslinked hydrogel, OHA-PBA/PVA/Gen, which incorporates the antibiotic gentamicin (Gen) as a dynamic crosslinker. The hydrogel is formed through the formation of Schiff base bonds between phenylboronic acid-grafted oxidized hyaluronic acid (OHA-PBA) and Gen, as well as boronic acid ester bonds between OHA-PBA and polyvinyl alcohol (PVA). This unique composition imparts tissue adhesiveness, injectability and self-healing property to the hydrogel. The hydrogel also exhibits pH-responsive antibiotic release behavior due to the acid-responsive dissociation of Schiff base bonds. As a result, it demonstrates strong antibacterial activity against both Gram-positive bacteria <em>S. aureus</em> and Gram-negative bacteria <em>E. coli</em> through contact killing and diffusion killing mechanisms. Importantly, the OHA-PBA/PVA/Gen hydrogel avoids incorporation of toxic small molecular crosslinking agents, and all the components of the hydrogel are biocompatible, ensuring its biosafety. In a <em>S. aureus</em>-infected wound mouse model, this hydrogel effectively eradicated bacteria and promoted angiogenesis, leading to significantly accelerated wound healing. These results highlight the potential of the dual dynamically crosslinking hydrogel OHA-PBA/PVA/Gen as a multifunctional wound dressing for the treatment of bacteria-infected wound.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A multifunctional hydrogel dressing loaded with antibiotics for healing of infected wound\",\"authors\":\"\",\"doi\":\"10.1016/j.ijpharm.2024.124770\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Wound bacterial infections can significantly delay the healing process and even lead to fetal sepsis. There is a need for multifunctional dressings that possess antibacterial property, tissue adhesive property, self-healing capability, and biocompatibility to effectively treat bacteria-infected wound. In this study, we report a dual dynamically crosslinked hydrogel, OHA-PBA/PVA/Gen, which incorporates the antibiotic gentamicin (Gen) as a dynamic crosslinker. The hydrogel is formed through the formation of Schiff base bonds between phenylboronic acid-grafted oxidized hyaluronic acid (OHA-PBA) and Gen, as well as boronic acid ester bonds between OHA-PBA and polyvinyl alcohol (PVA). This unique composition imparts tissue adhesiveness, injectability and self-healing property to the hydrogel. The hydrogel also exhibits pH-responsive antibiotic release behavior due to the acid-responsive dissociation of Schiff base bonds. As a result, it demonstrates strong antibacterial activity against both Gram-positive bacteria <em>S. aureus</em> and Gram-negative bacteria <em>E. coli</em> through contact killing and diffusion killing mechanisms. Importantly, the OHA-PBA/PVA/Gen hydrogel avoids incorporation of toxic small molecular crosslinking agents, and all the components of the hydrogel are biocompatible, ensuring its biosafety. In a <em>S. aureus</em>-infected wound mouse model, this hydrogel effectively eradicated bacteria and promoted angiogenesis, leading to significantly accelerated wound healing. These results highlight the potential of the dual dynamically crosslinking hydrogel OHA-PBA/PVA/Gen as a multifunctional wound dressing for the treatment of bacteria-infected wound.</div></div>\",\"PeriodicalId\":14187,\"journal\":{\"name\":\"International Journal of Pharmaceutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Pharmaceutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0378517324010044\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Pharmaceutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0378517324010044","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
伤口细菌感染会严重延缓伤口愈合,甚至导致胎儿败血症。因此,需要具有抗菌性、组织粘附性、自愈合能力和生物相容性的多功能敷料来有效治疗细菌感染的伤口。在本研究中,我们报告了一种双重动态交联水凝胶 OHA-PBA/PVA/Gen,其中加入了抗生素庆大霉素(Gen)作为动态交联剂。这种水凝胶是通过苯硼酸接枝的氧化透明质酸(OHA-PBA)与 Gen 之间形成的席夫碱键以及 OHA-PBA 与聚乙烯醇(PVA)之间的硼酸酯键形成的。这种独特的成分赋予了水凝胶组织粘附性、注射性和自愈性。由于席夫碱键的酸响应解离作用,这种水凝胶还具有酸碱响应的抗生素释放特性。因此,通过接触杀灭和扩散杀灭机制,它对革兰氏阳性菌金黄色葡萄球菌和革兰氏阴性菌大肠杆菌都具有很强的抗菌活性。重要的是,OHA-PBA/PVA/Gen 水凝胶避免了加入有毒的小分子交联剂,而且水凝胶的所有成分都具有生物相容性,确保了其生物安全性。在金黄色葡萄球菌感染的小鼠伤口模型中,这种水凝胶能有效消灭细菌并促进血管生成,从而显著加快伤口愈合。这些结果凸显了双重动态交联水凝胶 OHA-PBA/PVA/Gen 作为多功能伤口敷料治疗细菌感染伤口的潜力。
A multifunctional hydrogel dressing loaded with antibiotics for healing of infected wound
Wound bacterial infections can significantly delay the healing process and even lead to fetal sepsis. There is a need for multifunctional dressings that possess antibacterial property, tissue adhesive property, self-healing capability, and biocompatibility to effectively treat bacteria-infected wound. In this study, we report a dual dynamically crosslinked hydrogel, OHA-PBA/PVA/Gen, which incorporates the antibiotic gentamicin (Gen) as a dynamic crosslinker. The hydrogel is formed through the formation of Schiff base bonds between phenylboronic acid-grafted oxidized hyaluronic acid (OHA-PBA) and Gen, as well as boronic acid ester bonds between OHA-PBA and polyvinyl alcohol (PVA). This unique composition imparts tissue adhesiveness, injectability and self-healing property to the hydrogel. The hydrogel also exhibits pH-responsive antibiotic release behavior due to the acid-responsive dissociation of Schiff base bonds. As a result, it demonstrates strong antibacterial activity against both Gram-positive bacteria S. aureus and Gram-negative bacteria E. coli through contact killing and diffusion killing mechanisms. Importantly, the OHA-PBA/PVA/Gen hydrogel avoids incorporation of toxic small molecular crosslinking agents, and all the components of the hydrogel are biocompatible, ensuring its biosafety. In a S. aureus-infected wound mouse model, this hydrogel effectively eradicated bacteria and promoted angiogenesis, leading to significantly accelerated wound healing. These results highlight the potential of the dual dynamically crosslinking hydrogel OHA-PBA/PVA/Gen as a multifunctional wound dressing for the treatment of bacteria-infected wound.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.