Design of Chitosan-Coated CeO₂-Doped ZnCr LDO Nanocomposites for Optimized Azithromycin Delivery: A Kinetic and Mechanistic Perspective

Abstract

Traditional ways of formulating azithromycin are characterized by low oral bioavailability. Therefore, the development of new formulations to enhance drug bioavailability is crucial. The current study aims to evaluate the in vitro kinetics and sustained release of azithromycin (AZM) from a newly designed CS/CeO2@ZnCr LDO glycerosomes incorporating Chitosan, soy lecithin, and glycerol. Various analytical techniques, including Fourier Transform Infrared Spectroscopy (FTIR), Brunauer-Emmett-Teller (BET) analysis, Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), and zeta potential measurements, were employed for analysis. After two hours, 70.9% of the drug was released from CS/CeO2@ZnCr LDO glycerosomes at pH 7.4 (PBS), which can be attributed to their good swelling properties at various pH levels, temperatures, and time intervals. Kinetic analysis revealed that the Peppas-Sahlin model provided the best fit, with a release exponent (m) of 0.805 at pH 7.4, indicating an anomalous (non-Fickian) drug release mechanism. The Peppas-Sahlin and Weibull models were identified as the best fits for the sustained release data. Cytotoxicity assessments revealed that at a lower concentration of 2.5 μM, chitosan/CeO₂@ZnCr LDO glycerosomes/AZM exhibited no toxicity to the cells over 24 hours, suggesting that this concentration is suitable for further research. Furthermore, at a concentration of 6 mg/ml, chitosan/CeO₂@ZnCr LDO demonstrated enhanced efficiency against gram-negative bacteria compared to gram-positive bacteria when compared to CeO₂@ZnCr LDO. This study highlights the potential of this system to improve the therapeutic efficacy of azithromycin, particularly in the treatment of complex infections, while also offering a straightforward and scalable formulation approach for clinical translation.