ACS Appl Mater Interfaces. 2019 Apr 24;11(16):14640-14646. doi: 10.1021/acsami.9b02578. Epub 2019 Apr 12.
Current treatments of bacterial biofilms are limited by the poor penetration of antibiotics through their physical barrier as well as significant off-target toxicity of antibiotics and the induction of antibiotic resistance. Here we report a microneedle patch-mediated treatment for the effective elimination of biofilms by penetrating the biofilm and specifically delivering antibiotics to regions of active growth. We fabricated patches with self-dissolvable microneedles and needle tips loaded with chloramphenicol (CAM)-bearing and gelatinase-sensitive gelatin nanoparticles (CAM@GNPs). During the microneedle patch-mediated treatment, arrays of 225 microneedles simultaneously penetrate the biofilm matrix. Once inside, the microneedles dissolve and uniformly release CAM@GNPs into the surrounding area. In response to the gelatinase produced by the active bacterial community, the CAM@GNPs disassemble and release CAM into these active regions of the biofilm. Moreover, CAM@GNPs exhibited minimal off-target toxicity compared to direct CAM administration, which in turn favors wound healing. Importantly, we found that our microneedle-mediated treatment is more effective in treating Vibrio vulnificus biofilms than drug in free solution. We believe this new treatment strategy can be used to improve the delivery of a wide range of antimicrobial agents to biofilm-contaminated sites.
目前，细菌生物膜的治疗方法受到抗生素透过其物理屏障的渗透性差、抗生素的显著非靶向毒性以及抗生素耐药性的诱导的限制。在这里，我们报告了一种通过穿透生物膜并将抗生素专门递送到活跃生长区域来有效消除生物膜的微针贴片介导的治疗方法。我们使用可自溶解的微针和载有氯霉素（CAM）的、明胶酶敏感的明胶纳米颗粒（CAM@GNPs）的针尖制造了贴片。在微针贴片介导的治疗过程中，225 个微针阵列同时穿透生物膜基质。一旦进入，微针溶解并将 CAM@GNPs 均匀地释放到周围区域。响应活性细菌群落产生的明胶酶，CAM@GNPs 分解并将 CAM 释放到生物膜的这些活跃区域。此外，CAM@GNPs 表现出比直接 CAM 给药更小的非靶向毒性，这有利于伤口愈合。重要的是，我们发现我们的微针介导的治疗方法比游离药物更有效地治疗创伤弧菌生物膜。我们相信这种新的治疗策略可以用于改善将广泛的抗菌剂递送到生物膜污染部位的效果。
