Dey Rajib, Mukherjee Riya, Biswas Sucheta, Haldar Jayanta
Antimicrobial Research Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India.
School of Advanced Materials, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 560064, Karnataka, India.
ACS Appl Mater Interfaces. 2024 Jul 24;16(29):37795-37805. doi: 10.1021/acsami.4c09820. Epub 2024 Jul 15.
Biofilm-mediated wound infections pose a significant challenge due to the limitations of conventional antibiotics, which often exhibit narrow-spectrum activity, fail to eliminate recurrent bacterial contamination, and are unable to penetrate the biofilm matrix. While the search for alternatives has explored the use of metal nanoparticles and synthetic biocides, these solutions often suffer from unintended toxicity to surrounding tissues and lack controlled administration and release. In this study, we engineered a pH-responsive release-active dressing film based on carboxymethyl cellulose, incorporating a synthetic antibacterial molecule (SAM-17). The dressing film exhibited optimal mechanical stability for easy application and demonstrated excellent fluid absorption properties, allowing for prolonged moisturization at the site of injury. The film exhibited pH-dependent release of cargo, with 78% release within 24 h at acidic pH, enabling targeted antibacterial drug delivery within the wound microenvironment. Furthermore, the release-active film effectively eliminated repeated challenges of bacterial contamination. Remarkably, the film demonstrated a minimal toxicity profile in both in vitro and in vivo models. The film eliminated preformed bacterial biofilms, achieving a reduction of 2.5 log against methicillin-resistant (MRSA) and 4.1 log against vancomycin-resistant (VRSA). In a biofilm-mediated MRSA wound infection model, this release-active film eradicated the biofilm-embedded bacteria by over 99%, resulting in accelerated wound healing. These findings highlight the potential of this film as an effective candidate for tackling biofilm-associated wound infections.
生物膜介导的伤口感染由于传统抗生素的局限性而构成重大挑战，传统抗生素往往具有窄谱活性，无法消除反复出现的细菌污染，且无法穿透生物膜基质。虽然寻找替代方案的探索涉及使用金属纳米颗粒和合成杀菌剂，但这些解决方案往往对周围组织具有意外的毒性，并且缺乏可控的给药和释放。在本研究中，我们基于羧甲基纤维素设计了一种pH响应释放活性敷料膜，其中掺入了一种合成抗菌分子（SAM-17）。该敷料膜表现出最佳的机械稳定性以便于应用，并展示出优异的流体吸收性能，能够在损伤部位实现长时间保湿。该膜表现出货物的pH依赖性释放，在酸性pH下24小时内释放78%，从而能够在伤口微环境中实现靶向抗菌药物递送。此外，这种释放活性膜有效地消除了细菌污染的反复挑战。值得注意的是，该膜在体外和体内模型中均表现出最小的毒性特征。该膜消除了预先形成的细菌生物膜，对耐甲氧西林金黄色葡萄球菌（MRSA）的减少量达到2.5个对数，对耐万古霉素金黄色葡萄球菌（VRSA）的减少量达到4.1个对数。在生物膜介导的MRSA伤口感染模型中，这种释放活性膜根除了嵌入生物膜的细菌达99%以上，从而加速了伤口愈合。这些发现突出了这种膜作为解决与生物膜相关的伤口感染的有效候选物的潜力。
