title: In vitro characterization of pH-sensitive azithromycin-loaded methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) micelles.
abstract: In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5.5-7.8. It could control drug in vitro release and demonstrate higher release rate at pH 6.0 than that at pH 7.4. In vitro antibacterial experiment indicated that the activity of azithromycin-loaded micelles against S. aureus was superior to free azithromycin in medium at both pH 6.0 and pH 7.4. Using fluorescein as substitute with pH-dependent fluorescence decrease property, laser confocal fluorescence microscopy analysis confirmed that cellular uptake of micelles was improved due to protonation of copolymer's imidazole groups at pH 6.0. The enhanced cellular uptake and release of drug caused its activity enhancement in acidic medium when compared with free drug. The micellar drug delivery system should be potential application in the field of bacterial infection treatment.
authors.affiliation: School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, No. 16866 East Road of Jingshi, Jinan 250200, Shandong Province, PR China; Shandong Academy of Medical Sciences, No. 18877 Jingshi Road, Jinan 250062, Shandong Province, PR China. Electronic address: 774023681@qq.com.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Teng
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China. Electronic address: 1475110416@qq.com.
authors.forename: Peizong
authors.initials: P
authors.lastname: Deng
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China. Electronic address: zhimei_song@126.com.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Song
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China. Electronic address: 2468161542@qq.com.
authors.forename: Feilong
authors.initials: F
authors.lastname: Zhou
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China. Electronic address: runliangfeng@126.com.
authors.forename: Runliang
authors.initials: R
authors.lastname: Feng
authors.affiliation: School of Biological Science and Technology, University of Jinan, No. 336 West Road of Nanxinzhuang, Jinan 250022, Shandong Province, PR China. Electronic address: mls_liun@ujn.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
mesh_terms: D001224:Aspartic Acid / Q000737:chemistry*; D017963:Azithromycin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry*; D008823:Micelles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D004337:Drug Carriers; D007093:Imidazoles; D008823:Micelles; D001224:Aspartic Acid; D011092:Polyethylene Glycols; D017963:Azithromycin
keywords: Azithromycin; Methoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole); Micelles; S. aureus