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.
Keywords: Cholesteryl hemisuccinate; clarithromycin; drug loading; ion pair; irritation; liposomes.