Wounds or tissue openings in the skin are susceptible to bacterial attack, which can deteriorate and slow down the healing process. In this regard, antimicrobial gels are valuable as they mitigate the infection spread and assist in the healing. Despite the success, commercially available release-active antimicrobial gels suffer from narrow-spectrum activity, resistance induction, reservoir exhaustion, and in some cases may be associated with toxicity. To circumvent these limitations, herein, we have developed new quaternary lipophilic chitosan derivatives (QuaChi) synthesized by modifying the primary alcohol of the sugar moieties without altering the free amino groups of glucosamines. Compared to protonated chitosan, the synthesized derivatives exhibited improved water solubility and enhanced antibacterial activity against multidrug-resistant Gram-positive and Gram-negative bacteria including clinical isolates. The enhanced antibacterial activity was evident from the bacterial membrane depolarization leading to rapid inactivation of ∼10⁵–10⁶ bacterial cells within 2 h. The applicability of the chitosan derivatives was further demonstrated by developing antibacterial hydrogels by cross-linking the free amino groups of QuaChi with biocompatible gelatin through amide linkages. The hydrogel showed ∼5–7 log reduction of various multidrug-resistant bacteria including the stationary-phase cells within 6 h. Scanning electron microscopy revealed the loss of integrity of the bacterial structure when treated with the hydrogel, whereas mammalian cells (human embryonic kidney-293 (HEK-293)), when exposed to the hydrogel, appeared to be healthy with retained morphology. Collectively, these findings suggest that the developed hydrogel formulation can find potential applications to combat notorious drug-resistant bacterial infections in the healthcare settings.

中文翻译：

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第四季度亲脂性壳聚糖和明胶交联的抗菌水凝胶有效地杀死多药耐药细菌，对哺乳动物细胞的毒性最小。

皮肤上的伤口或组织开口易受细菌侵袭，这可能会使细菌恶化并减慢愈合过程。在这方面，抗微生物凝胶是有价值的，因为它们减轻了感染的传播并有助于治愈。尽管取得了成功，但是市售的具有释放活性的抗微生物凝胶仍具有窄谱活性，抗药性，储库耗尽，并且在某些情况下可能与毒性有关。为了避免这些限制，在这里，我们开发了新的季脂亲性壳聚糖衍生物（QuaChi）是通过修饰糖部分的伯醇而不改变葡糖胺的游离氨基而合成的。与质子化壳聚糖相比，合成衍生物对包括临床分离株在内的多药耐药革兰氏阳性和革兰氏阴性细菌表现出改善的水溶性和增强的抗菌活性。细菌膜去极化导致2小时内约10 ⁵ –10 ^6个细菌细胞快速失活，从而明显增强了抗菌活性。通过将QuaChi的游离氨基交联来开发抗菌水凝胶，进一步证明了壳聚糖衍生物的适用性。通过酰胺键具有生物相容性的明胶。水凝胶在6小时内显示出包括固定相细胞在内的多种耐多药细菌减少了约5-7 log。扫描电子显微镜显示当用水凝胶处理时细菌结构完整性的丧失，而当暴露于水凝胶时哺乳动物细胞（人类胚胎肾293（HEK-293））看起来是健康的，并具有保留的形态。总的来说，这些发现表明，所开发的水凝胶制剂可以在医疗机构中找到对抗臭名昭著的耐药细菌感染的潜在应用。