Preparation, characterization and toxicological evaluation of azithromycin-loaded chitosan nanoparticles alone and in combination with cetirizine dihydrochloride

Abstract

Respiratory tract infections are becoming difficult to treat due to multidrug resistance (MDR) bacteria. Nanoparticles (NPs) are suitable substitutes to circumvent MDR. This study was designed to formulate, characterize, and investigate the safety evaluation of azithromycin-loaded chitosan nanoparticles (AZM-CSNPs). AZM-CSNPs were prepared using the ionic gelation method and were characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FT-IR), zeta potential, entrapment efficiency, and in vitro drug release. Genotoxic and cytotoxic activity was determined by COMET and MTT assays. The practical yield of NPs was 77%. FT-IR illustrated the peak appearance at 1638 cm-1, representing the formation of NPs. The bending of spectrum at 1525 cm-1 corresponds to chemical cross-linking with polymer attributing C-N bonds. The average size of nanoparticles was 64 nm with a zeta potential of +26.5mV and polydispersity index of 0.214, which expresses good stability. SEM image exhibited nearly spherical-shaped NPs owning smooth surfaces with entrapment efficiency of 71.14%. Chitosan nanoparticles bestow maximum drug release at acidic pH. The general release profile of the drug was divided into two basic phases: 10% initial burst release at 10hrs then a gradual release after 24hrs. Furthermore, the outcome elucidates that AZM-CSNPs do not cause DNA damage and there was no cytotoxic effect observed on Vero cell lines. Our results revealed that the combination of AZM-CSNPs with cetirizine dihydrochloride may be considered an innovative and promising strategy to improve the efficacy and targeted drug delivery and thus could be an effective approach to prevail over azithromycin resistance.