Liu Chunmei, Shi Jing, Dai Qingyun, Yin Xiaoxing, Zhang Xiaoyan, Zheng Aiping
Department of Pharmaceutics, School of Pharmacy, Medical University of Hebei Province , Shijiazhuang , P.R. China .
Drug Dev Ind Pharm. 2015 Feb;41(2):272-8. doi: 10.3109/03639045.2013.858740. Epub 2013 Nov 19.
The aim of this study was to investigate the ciprofloxacin liposome of high encapsulation efficiency with optimal physical properties for pulmonary administration and to test its in-vivo potential in rats.
Ciprofloxacin-loaded liposome was prepared by gradient of ammonium sulfate method. The particle size and morphology were determined using a NANOPHOX particle size analyzer and a transmission electron microscope, respectively. Encapsulation efficiency was calculated by UV spectrophotometry. Ciprofloxacin liposome released in vitro was performed using simulated lung fluid. In-vivo studies, pharmacokinetics and pulmonary distribution, HPLC method was established to determine the concentration of ciprofloxacin in rat plasma and lung tissue. The pulmonary pathological section was used to observe the change of pulmonary pathology.
The optimized ciprofloxacin liposome, which had a high encapsulation efficiency of 93.96%, and an average particle size of 349.6 nm with a span of 0.42, showed sustained in-vitro release. The optimized ciprofloxacin liposome was further examined in the in-vivo study in rats. The concentration of ciprofloxacin in lung and blood was simultaneously determined in each rat. The ratio of the AUClung value between ciprofloxacin liposome and ciprofloxacin solution was 288.33, whereas the relative bioavailability was 72.42%, and the drug targeting efficiency of ciprofloxacin liposome and ciprofloxacin solution by intratracheal administration were 799.71 and 2.01, respectively.
Ciprofloxacin liposome for pulmonary administration offered an attractive alternative that was able to deliver high concentrations of antibiotic directly to the chosen target site while minimizing the local irritation.
本研究旨在制备具有高包封率且物理性质适合肺部给药的环丙沙星脂质体，并在大鼠体内测试其应用潜力。
采用硫酸铵梯度法制备载环丙沙星脂质体。分别使用NANOPHOX粒度分析仪和透射电子显微镜测定粒径和形态。通过紫外分光光度法计算包封率。使用模拟肺液进行环丙沙星脂质体的体外释放实验。在体内研究、药代动力学和肺部分布方面，建立高效液相色谱法测定大鼠血浆和肺组织中环丙沙星的浓度。利用肺部病理切片观察肺部病理变化。
优化后的环丙沙星脂质体包封率高达93.96%，平均粒径为349.6nm，跨距为0.42，呈现体外缓释特性。在大鼠体内研究中对优化后的环丙沙星脂质体进行了进一步考察。同时测定每只大鼠肺组织和血液中环丙沙星的浓度。环丙沙星脂质体与环丙沙星溶液的肺组织药时曲线下面积（AUClung）比值为288.33，相对生物利用度为72.42%，经气管给药后环丙沙星脂质体和环丙沙星溶液的药物靶向效率分别为799.71和2.01。
肺部给药的环丙沙星脂质体是一种有吸引力的选择，能够将高浓度抗生素直接递送至选定的靶部位，同时将局部刺激降至最低。
