Polymeric inserts containing azithromycin-loaded Eudragit^® L100 nanoparticles were developed to sustain the drug release and enhance its ocular performance. The solvent diffusion technique was employed to prepare nanoparticles. The developed nanoparticles (NPs) were fully characterized and investigated. The solvent casting method was used to prepare azithromycin ocular inserts (azithromycin, AZM film) by adding hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC) solutions after the incorporation of AZM-loaded Eudragit^® L100 nanoparticles into plasticized PVA (polyvinyl alcohol) solutions. The optimized nanoparticles had a particle size of 78.06 ± 2.3 nm, zeta potential around −2.45 ± 0.69 mV, polydispersity index around 0.179 ± 0.007, and entrapment efficiency 62.167 ± 0.07%. The prepared inserts exhibited an antibacterial effect on Staphylococcus aureus and Escherichia coli cultures. The inserts containing AZM-loaded nanoparticles showed a burst release during the initial hours, followed by a sustained drug release pattern. Higher cumulative corneal permeations from AZM films were observed for the optimized formulation compared to the drug solution in the ex-vivo trans-corneal study. In comparison to the AZM solution, the inserts significantly prolonged the release of AZM in rabbit eyes (121 h). The mucoadhesive inserts containing azithromycin-loaded Eudragit^® L100 nanoparticles offer a promising approach for the ocular delivery of azithromycin (antibacterial and anti-inflammatory) to treat ocular infections that require a prolonged drug delivery.

The fast elimination of drugs from the cornea is one of many challenges associated with the topical administration of conventional dosage forms. The present manuscript aimed to prepare modified-release inserts containing erythromycin (ERY) to enhance drug delivery and address the aforementioned limitation. Film formulations were developed using Eudragit^® L100 (EUD) and Polyvinyl Alcohol (PVA) polymers. ERY-loaded EUD-based nanoparticles were developed by the colloidal dispersion method using PVA as the emulsifier. The film-casting method was applied to form the mucoadhesive films using sodium alginate, gelatin, cyclodextrin-α, and β as polymeric film matrices. Different physicochemical properties of the optimized formulations and in vitro release profiles were evaluated. The in vivo evaluation was performed by collecting tear samples of rabbits using a novel, non-invasive method following the administration of inserts in the cul-de-sac. The ERY amount was assayed using a microbiological assay. The developed films showed prolonged in vitro and in vivo release profiles over five to six days; they had suitable physicochemical properties and a tensile strength of 2–3 MPa. All formulations exhibited antibacterial efficacy against E. coli and S. aureus with more than 20 mm diameter of inhibited growth zones. None of the formulations caused irritation to the rabbit’s eye. The inserts showed promising pharmacokinetics with AUC_0–120 of 30,000–36,000 µg·h/mL, a C_max of more than 1800 µg/mL at 4 h, and maintained drug concentration over the threshold of 5 µg/mL during the following 120 h of study. Nanoparticle-containing, mucoadhesive films could be fabricated as ocular inserts and can prolong the topical ocular delivery of ERY.

Conventional anti-infective eye drops are the most common forms of drugs prescribed for the management of topical ocular infections. Despite their convenience, topical eye drops face multiple challenges, including limited bioavailability and repetitive administration. The present study aimed to prepare, evaluate, and compare film-structured and nanofibrous ocular inserts using biocompatible polymers of polyvinyl alcohol (PVA) and polycaprolactone (PCL) to achieve sustained ciprofloxacin Hydrochloride (CIP) delivery. The nanofibrous formulations were prepared by electrospinning and glutaraldehyde crosslinking while the film formulation was prepared by solvent casting. Nanofibrous inserts had mean diameters in the range 330–450 nm. Both film and nanofibrous inserts were strong, although the nanofibers had higher flexibility. In vitro antibacterial efficacy against Staphylococcus aureus and Escherichia coli was observed for all formulations and cell viability of more than 70% confirmed their non-toxicity. In vitro release studies showed prolonged release of 2 days for the film and 5 days for the nanofibers compared with a 10-h release of CIP from the eye drop. Pharmacokinetic studies of rabbits’ eyes showed 4.5–5-folds higher AUC for the nanofiber formulations compared with the eye drop. Thus, prolonged-release film-structured and nanofibrous inserts are suitable carriers for ocular delivery of CIP.

Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 μg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC_0-144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.

The present study aimed to prepare nanofibrous inserts for sustained ocular drug delivery of Azithromycin (AZM) toward conquering the obstacles of conventional topical drug delivery. Nanofibers were fabricated by electrospinning using polycaprolactone (PCL) and cellulose acetate (CA) which are biocompatible and biodegradable polymers. Prepared nanofibers were evaluated in terms of physicochemical, morphological properties, pharmacokinetic study and ocular irritation. SEM images revealed average diameters of about 160 nm and 190 nm for CA and PCL nanofibers, respectively. These ocular drug delivery systems were strong, flexible, and stable under humid and dry conditions. Quantification was performed using microbiological assay by M. luteus as a microorganism. While PCL-based nanofibrous inserts released AZM in a two-step manner initiated by a burst release via Peppas kinetical model, CA-based inserts showed a gradual release profile without any burst release which followed the first-order model. Results showed that these inserts were non-cytotoxic and non-irritating. The nanofibers showed antibacterial efficacy against Escherichia coli and Staphylococcus aureus. In addition, according to a pharmacokinetic study in Rabbit's Eye, a higher C_max and lower T_max were achieved by PCL nanofibers compared to CA-based ones. The pharmacokinetic study of nanofibers in rabbit eyes showed that all formulations were able to maintain the effective concentration of AZM for about 6 days. In conclusion, the prepared nanofibers can be effectively utilized for prolonged ocular delivery of AZM in the treatment of conjunctival infections.

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.