National Engineering Research Centre of Immunological Products & Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
National Engineering Research Centre of Immunological Products & Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
Biomater Adv. 2022 Sep;140:213029. doi: 10.1016/j.bioadv.2022.213029. Epub 2022 Aug 3.
Wound infections, especially infections with multidrug-resistant bacteria, are a serious public health issue worldwide. In addition, the accumulation microbial biofilm of multidrug-resistant Pseudomonas aeruginosa increases the risk and physically obstruct its healing activity at the wound site. Therefore, the development of an eminent agent to control wound infection is urgently needed. Here, we report a novel chitosan (a natural biological macromolecule)-modified self-nanoemulsifying system (CSN) with lipophilic chlorhexidine acetate (CAA, a poorly water-soluble agent) that was designed and prepared using low-energy emulsification methods. We found that CSN displays better antibacterial efficacy, which occurs more quickly than its aqueous solution, in destroying the structure of the bacterial cell membrane and promoting the leakage of nucleic acids, proteins, K, and Mg from Pseudomonas aeruginosa cells. Importantly, CSN also accelerates skin wound healing after Pseudomonas aeruginosa infection by inhibiting biofilm formation and eradicating mature biofilms. Moreover, the proteomic results suggested that CSN altered membrane permeability and cellular membrane metabolism, allowing more drug molecules to enter the cytosol. Based on these results, this lipophilic self-nanoemulsifying system may be applied in the treatment of skin wounds caused by multidrug-resistant bacteria, especially Pseudomonas aeruginosa.
伤口感染，特别是耐多药细菌感染，是一个全球性的严重公共卫生问题。此外，耐多药铜绿假单胞菌积累的微生物生物膜增加了感染风险，并在伤口部位物理性阻碍其愈合活性。因此，迫切需要开发一种卓越的药物来控制伤口感染。在这里，我们报告了一种新型壳聚糖（一种天然生物大分子）修饰的自微乳给药系统（CSN），它含有疏水性醋酸氯己定（CAA，一种水溶性差的药物），是使用低能量乳化方法设计和制备的。我们发现 CSN 在破坏细菌细胞膜结构和促进铜绿假单胞菌细胞内核酸、蛋白质、K 和 Mg 泄漏方面，比其水溶液具有更好的抗菌效果，且起效更快。重要的是，CSN 还通过抑制生物膜形成和根除成熟生物膜来加速铜绿假单胞菌感染后的皮肤伤口愈合。此外，蛋白质组学结果表明，CSN 改变了膜通透性和细胞膜代谢，使更多的药物分子进入细胞质。基于这些结果，这种疏水性自微乳给药系统可能应用于治疗耐多药细菌，特别是铜绿假单胞菌引起的皮肤伤口。
