Preparation of Azithromycin Nanofibers as Controlled Release Ophthalmic Drug Carriers Using Electrospinning Technique: In-Vitro and in-Vivo Characterization

Abstract

Purpose: Conventional topical dosage forms face with some challenges like low intraocular bioavailability, which could be overcome by application of novel drug delivery systems. Therefore, this study was conducted to prepare azithromycin (AZM)-loaded chitosan/polyvinyl alcohol/polyvinyl pyrrolidone (CS/PVA-PVP) nanofibers with the prolonged antibacterial activity by electrospinning method. Methods: After preparation of nanofibers, they were characterized in terms of physicochemical and morphological properties. In-vitro and in –vivo release of the drug from nanofibers were evaluated using microbial assay against the Micrococcus luteus. Antibacterial efficacy of the nanofibers was assessed. The ophthalmic irritation test was also performed. MTT test was carried out to evaluate cytotoxicity of the formulations. Results: All the formulations were found to be stable with uniform thickness, weight, and drug content. Nanofibers had a diameter range from 119±29 to 171±39 nm. The inserts were non-irritant and non-toxic to the rabbits҆ eye. Based on the obtained results, the crosslinked AZM nanofibers showed slower and more controlled drug release in tear fluid compared to the non-crosslinked ones, within 184 h. Conclusion: Our results revealed that the prepared nanofibers could be considered as suitable and non-invasive inserts for the prolonged ophthalmic delivery of azithromycin.

Preparation and Evaluation of Nanofibrous and Film-Structured Ciprofloxacin Hydrochloride Inserts for Sustained Ocular Delivery: Pharmacokinetic Study in Rabbit’s Eye

“…We obtained similar results in our previous study, where GA-crosslinking led to formation of a network-chain structure with a lower degree of swelling and decreased the amount of released azithromycin and eliminated the burst phase. Therefore, the release of azithromycin was slower in cases with crosslinked fibers compared with non-crosslinked formulations [8].…”

“…The lower strength of CIP-F could be attributed to the preparation process. On the other hand, the GA-crosslinked CIP-OG nanofiber had a higher tensile strength compared with the non-crosslinked CIP-O because of the development of a rigid bonding network between fibers at intersections which could enhance the mechanical properties of crosslinked nanofibers [8,27]. Determining the degree of swelling is crucial to understanding the drug release behavior of inserts.…”

“…Novel drug delivery systems such as ocular inserts and nano-structured preparations have been developed to overcome the common limitations of conventional ocular drug delivery systems by enhancing the drug's contact time with the cornea and increasing intraocular bioavailability [6,7]. One of the most important benefits of prepared inserts is the convenience and ease of administration to the conjunctival sac [6,8]. Nanofibrous inserts are one of the most favorable systems for topical ocular delivery owing to their unique properties such as high surface-to-volume ratio, porous structure, strength, flexibility, and the ability for controlled release of the drug [9].…”