A lipophilic chitosan-modified self-nanoemulsifying system influencing cellular membrane metabolism enhances antibacterial and anti-biofilm efficacy for multi-drug resistant Pseudomonas aeruginosa wound infection
A lipophilic chitosan-modified self-nanoemulsifying system influencing cellular membrane metabolism enhances antibacterial and anti-biofilm efficacy for multi-drug resistant Pseudomonas aeruginosa wound infection
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DOI：
10.1016/j.bioadv.2022.213029
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发表时间：
2022-09-01
影响因子：
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通讯作者：
Sun, Hongwu
中科院分区：
文献类型：
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作者：
Cai, Dingyi;Zhang, ZeLong;Sun, Hongwu
伤口感染，特别是耐多药细菌感染，是世界范围内严重的公共卫生问题。此外，多重耐药铜绿假单胞菌的微生物生物膜积累增加了风险，并在物理上阻碍了其在伤口部位的愈合活性。因此，迫切需要开发一种有效的药物来控制伤口感染。本文报道了一种新型的壳聚糖（一种天然生物大分子）修饰的自纳米乳化系统（CSN），该系统采用低能乳化方法设计和制备了亲脂性醋酸氯己定（CAA，一种低水溶性剂）。我们发现CSN在破坏细菌细胞膜结构，促进铜绿假单胞菌细胞中核酸、蛋白质、K+和Mg2+的渗漏方面表现出比水溶液更快的抗菌效果。重要的是，CSN还通过抑制生物膜的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改变了细胞膜的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，这种亲脂性自纳米乳化系统可能应用于多药耐药细菌，特别是铜绿假单胞菌引起的皮肤伤口的治疗。
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 in-creases 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 bio-logical 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 Mg2+ from Pseudomonas aeruginosa cells. Importantly, CSN also accelerates skin wound healing after Pseu-domonas 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.