A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC_0–96 for the nanofibers was 9–20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

The purpose of this study was to prepare poly (D-L) lactide-co-glycolide (PLGA) and poly ε-caprolactone (PCL) nanofibers containing metronidazole and amoxicillin using an electrospinning process as intrapocket sustained-release drug delivery systems for the treatment of periodontal diseases. Scanning electron microscopy showed that the drug containing PLGA and PCL nanofibers produced from the electrospinning process was uniform and bead-free in morphology. The obtained nanofibers had a strong structure and resisted external tension according to the tensiometry results. The cytotoxicity results indicated acceptable cell viability (>80%). Quantification by high-performance liquid chromatography showed almost complete in vitro drug release between 7 and 9 days, whereas 14 days were required for complete drug release in vivo. No significant signs of irritation or inflammatory reaction were detected after three weeks of subcutaneous implantation of nanofibers in the animal models, thus indicating suitable compatibility. The results therefore suggest that the designed nanofibers can be used as potential commercial formulations in the treatment of periodontitis as controlled-release intrapocket drug delivery systems that can increase patient compliance. This is due to their ability to reduce the frequency of administration from three times daily in a systemic manner to once weekly as local delivery.

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.

Purpose: The poor bioavailability of drugs in the ocular delivery systems is an important issue and development of delivery systems with prolonged release profile could be in a major importance. This study aims to develop an ocular delivery system using electrospun nanofibers to be a candidate insert for delivery of triamcinolone acetonide. Methods: For this purpose, three different chitosan-based formulations were prepared by electrospinning method, and electrospun nanofibers were compared to a formulation comprising hydrophobic polymers (Eudragit S100 and Zein). The electrospun nanofibers were characterized by SEM and FTIR analyses. The release profile and release kinetic models of all the formulations were also examined. Results: The SEM photographs of electrospun nanofibers revealed that among the four designed formulations, formulation obtained by electrospinning of chitosan and PVP possessed the best quality and the minimum size (120 ±30 nm) , which resulted the most uniform and bead-free nanofibers. This formulation also possessed the prolonged release profile of triamcinolone acetonide and was the only electrospun nanofiber following the zero-order kinetic profile. Due to the small diameter and uniformity of this formulation, the prolonged and well controlled release profile, it could be taken into account as a candidate to overcome the drawbacks of the commonly used ocular delivery systems and be used as ocular insert. Conclusion: This study confirmed the ability of electrospun nanofibers to be used as ocular inserts for delivery of ophthalmic drugs.

Ocular fungal infections affect more than one million people annually worldwide. They can lead to impaired vision or even complete blindness, so they should be treated immediately to prevent such consequences. Although topical administration has always been the most common route of ocular drug delivery owing to high patient acceptance, reduced side effects, and the possibility of self-administration, its limited ocular bioavailability poses a major challenge. As a result, attention has recently been drawn to the design and development of novel drug delivery systems (NDDS) that can overcome the challenges of conventional dosage forms. This research is the first to review and classify the studies which have designed and developed topical ocular NDDS with the aim to compare the performance and antifungal activity of these novel systems with conventional forms. According to the results, all studies seemed to confirm the superiority of NDDS over conventional forms in cases of released and permeated drug and antifungal activity. The NDDS were used specifically to improve ocular delivery by slowing down the release rate, increasing drug permeation, and subsequently increasing the antifungal effects of the active pharmaceutical ingredients. Hence, further studies on NDDS may aid the optimization of ocular drug delivery of antifungal drugs.