Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas aeruginosa

脂质体制剂中环丙沙星和粘菌素的共同递送可增强针对多药耐药铜绿假单胞菌的体外抗菌活性

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作者:Shaoning Wang, Shihui Yu, Yuwei Lin, Peizhi Zou, Guihong Chai, Heidi H Yu, Hasini Wickremasinghe, Nivedita Shetty, Junhong Ling, Jian Li, Qi Tony Zhou

Conclusions

Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.

Methods

Colistin (Col) and ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate gradient. Particle size, encapsulation efficiency, in vitro drug release and in vitro antibiotic activities were evaluated.

Purpose

This study aims to develop liposomal formulations containing synergistic antibiotics of colistin and ciprofloxacin for the treatment of infections caused by multidrug-resistant Pseudomonas aeruginosa.

Results

The optimized liposomal formulation has uniform sizes of approximately 100 nm, with encapsulation efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was independent of DMPG ratio. Incorporation of colistin significantly accelerated the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The cytotoxicity study using A549 cells showed the liposomal formulation is as non-toxic as the drug solutions. Liposomal formulations of combinations had enhanced in vitro antimicrobial activities against multidrug resistant P. aeruginosa than the monotherapies. Conclusions: Liposomal formulations of two synergistic antibiotics was promising against multidrug resistant P. aeruginosa infections.

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