Clarithromycin-loaded liposomes offering high drug loading and less irritation

Abstract The aim of this study was to develop an efficient method of preparing less irritant clarithromycin-loaded liposomes (CLA-Lip) for injection with a high drug loading and to evaluate their physicochemical characteristics before and after lyophilization. CLA-Lip were prepared using the film-dispersion method with sodium cholesterol sulfate (SCS) and n-hexyl acid as the regulators and then lyophilized. The liposomes were characterized in terms of their size, size distribution, zeta potential, morphology, in vitro release, haemolysis, and lyophilization and irritation testing was carried out. The TEM images revealed that the structure of the CLA-Lip were multilamellar and of a regular size of around 100 nm. In addition, the lyophilized CLA-Lip were characterized by DSC and Infrared spectroscopy to confirm the structure. H-bonding and salt-forming reactions were used to ensure that clarithromycin (CLA) was stably encapsulated in the liposomes. This method provided a 30-fold increase in the concentration of clarithromycin relative to that in aqueous solution. Sucrose was found to be the best protective agent and was added in an amount of 12.5% (w/v). According to the mouse scratch test and the rat paw lick test, the pain of CLA-Lip was significantly reduce by approximately 80% compared with the solution of clarithromycin phosphate. In addition, rabbit ear vein experiments produced similar results. These findings suggested that CLA-Lip was a stable delivery system with less irritation, which should be extremely suitable for clinical application.