title: Clarithromycin ion pair in a liposomal membrane to improve its stability and reduce its irritation caused by intravenous administration.
abstract: OBJECTIVE
  The aim of this study was to improve the drug loading (DL) and stability of clarithromycin (CLA)-loaded liposomes, and reduce the irritation caused by intravenous administration of CLA.
  
  
  METHODS
  A CLA-cholesteryl hemisuccinate (CHEMS) ion pair (CIP) was prepared by the solvent evaporation method and confirmed by fourier transform infrared spectroscopy, (1)H-nuclear magnetic resonance, differential scanning calorimetry and X-ray powder diffraction. Subsequently, CIP liposomes (CIP-Lip) were prepared by the thin-film dispersion method and evaluated in terms of their size, zeta-potential, in vitro release, stability, in vitro antimicrobial activity and irritation.
  
  
  RESULTS
  The CIP-Lip exhibited a homogeneous round shape, and their size, ζ-potential, encapsulation efficiency (EE) and DL were 71.89 ± 2.6 nm, -9.91 ± 0.82 mV, 95.1 ± 1.5% and 7.8 ± 0.3%, respectively. The physical appearance and drug content of CIP-Lip over a three-month storage remained almost unchanged. The release of CLA in CIP-Lip was pH-dependent, with a more rapid release at pH 6.0 than at pH 7.4. Although the in vitro antimicrobial activity of CIP-Lip was comparable with free CLA, the irritation produced by CIP-Lip was significantly reduced compared with CLA solution.
  
  
  CONCLUSIONS
  These findings suggest that CIP-Lip is a promising intravenous drug delivery system, especially on account of its high DL and reduced irritation.
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.|b Pharmaceutical Development Institute , Shanghai Hengrui Pharmaceutical Co., Ltd ., Shanghai , China.
authors.forename: Sicong
authors.initials: S
authors.lastname: Geng
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liu
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Hang
authors.initials: H
authors.lastname: Xu
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.|c National Post-doctoral Research Workstation , Jiangsu Kanion Pharmaceutical Co., Ltd ., Lianyungang , China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Helin
authors.initials: H
authors.lastname: Xu
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Gou
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Tian
authors.initials: T
authors.lastname: Yin
authors.affiliation: c National Post-doctoral Research Workstation , Jiangsu Kanion Pharmaceutical Co., Ltd ., Lianyungang , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.affiliation: a School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002788:Cholesterol Esters / Q000737:chemistry*; D017291:Clarithromycin / Q000737:chemistry*; D008081:Liposomes; D051379:Mice; D011817:Rabbits; D012756:Sheep
chemical_list: D002788:Cholesterol Esters; D008081:Liposomes; D017291:Clarithromycin; C013440:cholesteryl succinate
keywords: Cholesteryl hemisuccinate; clarithromycin; drug loading; ion pair; irritation; liposomes