Chitosan temperature-sensitive gel loaded with drug microspheres has excellent effectiveness biocompatibility and safety as an ophthalmic drug delivery system

摘要

In the present study, a temperature-sensitive gel composed of chitosan, carboxymethyl chitosan and glycerophosphate was prepared and loaded with chitosan microspheres encapsulating levofloxacin. The bioavailability of levofloxacin and the safety of this novel opthalmic drug delivery formulation were evaluated. Levofloxacin chitosan microspheres were prepared using the ionic gelation method, and the particle size and entrapment rate were determined. The morphology of the microspheres was observed by scanning electron microscopy. The pH and zeta potential were measured. The in vitro release of levofloxacin by the chitosan temperature-sensitive gel loaded with drug microspheres was determined using spectrophotometry. The eye retention time of the chitosan temperature-sensitive gel was calculated using a fluorescein sodium test. To assess the bioavailability and safety of the chitosan temperature-sensitive gel, a cell compatibility test, a cytotoxicity test and skin irritation test were performed. The entrapment rate of levofloxacin in the chitosan microspheres was determined to be 26.5%. The levofloxacin chitosan microspheres that were formed by chitosan and sodium tripolyphosphate were identified to be suitable for use in an ophthalmic particle dispersion system based on their physical and chemical properties. The pH of the levofloxacin chitosan microsphere suspension was 5.87±0.04, the average particle diameter was 2,452±342 nm, the polydispersity index was 0.168±0.028 and the ζ potential was 28.62±1.7 mV. The chitosan temperature-sensitive gel carrying microspheres loaded with drug prevented drug burst release at the initial stage and facilitated the slow release of the drug later on. Furthermore, this delivery system markedly prolonged the contact duration of levofloxacin with the eye. The chitosan temperature-sensitive hydrogel was safe and provided a good bioavailability of the drug. The results revealed that the chitosan temperature-sensitive gel had a cytotoxicity of grade 0, and no erythematous response was observed during the entire course of the skin irritation test. The present study provided a basis for the future development of the chitosan-based temperature-sensitive hydrogel in ophthalmic drug delivery.