载有不同表面电荷的替卡西林纳米脂质体对铜绿假单胞菌（ATCC 29248）的体外和体内活性。

In vitro and in vivo activities of ticarcillin-loaded nanoliposomes with different surface charges against Pseudomonas aeruginosa (ATCC 29248).

机构信息

Department of Laboratory Sciences, Borujerd Branch, Islamic Azad University, Borujerd, Iran.

出版信息

Daru. 2012 Oct 3;20(1):41. doi: 10.1186/2008-2231-20-41.

DOI:10.1186/2008-2231-20-41

PMID:23351156

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3555901/

Abstract

BACKGROUND

Pseudomonas aeruginosa exhibits multiple antibiotic resistance mechanisms. Different studies have shown that entrapment of antibiotics into liposomes could increase their anti-Pseudomonas activity. The objectives of this study were to prepare ticarcillin loaded-nanoliposomes with variable surface charges and evaluate their in vitro and in vivo efficacies against Pseudomonas aeruginosa (ATCC 29248).

METHODS

Ticarcillin-loaded nanoliposomes with positive, negative and neutral surface charges were prepared by extrusion method. Ticarcillin encapsulation efficacies for different formulations were measured by HPLC method. Minimum inhibitory concentration (MIC) of ticarcillin nanoliposomal forms against strain ATCC 29248 were determined by broth dilution method. The killing rate of Pseudomonas aeruginosa was exposed to various concentrations of ticarcillin in free and nanoliposomal forms were analyzed. Ultimately, in vivo therapeutic efficacy of nanoliposomes in burned mice skin infected with strain ATCC 29248 was investigated.

RESULTS

The encapsulation efficacies for ticarcillin-loaded cationic nanoliposomes were significantly higher (76% ± 0.17) than those of neutral (55% ± 0.14) and anionic (43% ± 0.14) nanoliposomes. The MIC of free, cationic, neutral and anionic nanoliposomal forms of ticarcillin against ATCC 29248 were to 24, 3, 6 and 48 mg/L, respectively. The killing rates of ticarcillin-loaded cationic nanoliposomes were higher than those of free and other drug formulations. Treatment by ticarcillin-loaded nanoliposomes with positive, neutral and negative surface charges resulted in almost 100, 60 and 20% survival rates, respectively.

CONCLUSION

Our data suggested that cationic ticarcillin-loaded nanoliposomes because of high effectiveness would be a good choice to treatment of Pseudomonas aeruginosa infections.

摘要

背景

铜绿假单胞菌表现出多种抗生素耐药机制。不同的研究表明，将抗生素包封在脂质体中可以提高其抗铜绿假单胞菌的活性。本研究的目的是制备具有不同表面电荷的替卡西林载纳米脂质体，并评估其对铜绿假单胞菌（ATCC 29248）的体外和体内疗效。

方法

采用挤出法制备带正、负、中性表面电荷的替卡西林载纳米脂质体。采用 HPLC 法测定不同制剂的替卡西林包封效率。采用肉汤稀释法测定替卡西林纳米脂质体形式对 ATCC 29248 株的最低抑菌浓度（MIC）。分析了替卡西林游离形式和纳米脂质体形式在不同浓度下对铜绿假单胞菌的杀菌率。最后，研究了替卡西林纳米脂质体在感染 ATCC 29248 株的烧伤小鼠皮肤中的体内治疗效果。

结果

替卡西林载阳离子纳米脂质体的包封效率明显高于中性（55%±0.14）和阴离子（43%±0.14）纳米脂质体（76%±0.17）。游离、阳离子、中性和阴离子替卡西林纳米脂质体形式对 ATCC 29248 的 MIC 分别为 24、3、6 和 48mg/L。替卡西林载阳离子纳米脂质体的杀菌率高于游离药物和其他药物制剂。带正、中、负表面电荷的替卡西林载纳米脂质体的治疗效果分别导致近 100%、60%和 20%的存活率。