Multidrug-resistant (MDR) Gram-negative bacteria (GNB), such as Acinetobacter and Klebsiella, are responsible for severe hospital-acquired infections. Colistin, despite its toxicity and low tissue penetration, is considered the last resort antibiotic against these microorganisms. Of concern, the use of Colistin has recently been compromised by the emergence of Colistin resistance. Herein, we developed a new formulation consisting of multifunctional chitosan-coated human albumin nanoparticles for the delivery of Colistin (Col/haNPs). Col/haNPs were in vitro characterized for encapsulation efficiency, drug release, stability and cytotoxicity and were evaluated for antibacterial activity against MDR GNB (Acinetobacter baumannii and Klebsiella pneumoniae). Col/haNPs showed sizes lower than 200 nm, high encapsulation efficiency (98.65%) and prolonged in vitro release of Colistin. The safety of the nanoformulation was demonstrated by a negligible cytotoxicity on human fibroblasts and hemolytic activity. Col/haNPs evidenced a high antibacterial effect with a significant decrease in MIC values compared to free Colistin, in particular against Col-resistant strains with a pronounced decline of bacterial growth over time. Moreover, Col/haNPs exhibited an inhibitory effect on biofilm formation that was 4 and 60 fold higher compared to free Colistin, respectively for Colistin susceptible and resistant A. baumannii. Our findings suggest that Col/haNPs could represent a promising Colistin nanocarrier with high antimicrobial activity on MDR GNB.

中文翻译：

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新型载粘菌素人白蛋白纳米颗粒增强抗菌和抗生物膜效果


多重耐药 (MDR) 革兰氏阴性菌 (GNB)，例如不动杆菌和克雷伯氏菌，是造成严重医院获得性感染的原因。尽管粘菌素具有毒性且组织渗透性低，但仍被认为是针对这些微生物的最后手段抗生素。令人担忧的是，粘菌素的使用最近因粘菌素耐药性的出现而受到影响。在此，我们开发了一种由多功能壳聚糖包被的人白蛋白纳米颗粒组成的新配方，用于递送粘菌素（Col/haNPs）。 Col/haNPs 在体外进行了包封效率、药物释放、稳定性和细胞毒性的表征，并评估了其对 MDR GNB（鲍曼不动杆菌和肺炎克雷伯菌）的抗菌活性。 Col/haNPs 的尺寸小于 200 nm，封装效率高 (98.65%)，粘菌素体外释放时间长。对人成纤维细胞的细胞毒性和溶血活性可忽略不计，证明了纳米制剂的安全性。 Col/haNPs 表现出较高的抗菌效果，与游离粘菌素相比，MIC 值显着降低，特别是针对 Col 耐药菌株，随着时间的推移，细菌生长明显下降。此外，对于粘菌素敏感和耐药的鲍曼不动杆菌，Col/haNPs 对生物膜形成的抑制作用分别比游离粘菌素高 4 倍和 60 倍。我们的研究结果表明，Col/haNPs 可以代表一种有前途的粘菌素纳米载体，对 MDR GNB 具有高抗菌活性。