Saba Mehrandish

Purpose: Chronic ailments usually decrease the quality of life due to the requirement for repetitive administration of drugs. Glaucoma is a chronic eye disease occurred because of increased intraocular pressure (IOP). Controlled-release inserts can overcome this challenge by a gradual release of the antiglaucoma drugs. This study aimed to fabricate ocular inserts of brimonidine tartrate (BMD) for the management of glaucoma. Methods: Different polymers including poly (D, L-lactide), polycaprolactone, cellulose acetate, and Eudragit RL100® were used to develop the BMD-loaded nanofibrous inserts by electrospinning technique. The inserts were characterized. The morphology and drug-polymer compatibility were examined by scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy and in vitro drug release in PBS. The IOP-lowering efficacy and irritancy of optimized formulation were assessed in the caprines. Results: SEM images demonstrated nanofibers with uniform morphology and a mean diameter<300 nm were fabricated. The nanofibers were high-strength and flexible enough to be placed in the conjunctival sac. FTIR showed drug-polymer compatibility. In vitro release study indicated a sustained-release profile of the drug during 6 days for inserts. In vivo evaluation indicated that the optimized formulation is capable of maintaining the IOP in a non-glaucomatous range for an extended duration of 6 days. In addition, the formulation was non-irritant to the caprine eye. Conclusion: Due to the prolonged IOP-lowering efficiency, BMD-loaded nanofibrous inserts can be considered suitable for the controlled release of drugs and thus enhance patient compliance by reducing the frequency of administration.

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.

Purpose: The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug. Methods: The oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE). Results: F7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model. Conclusion: The extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.

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.