Development and evaluation of polycaprolactone-based electrospun nanofibers containing timolol maleate as a sustained-release device for treatment of glaucoma: in vivo evaluation in equine eye.

Background and purpose: Prolonging the drug release can be a suitable approach to overcome the challenges related to topical ophthalmic administration of drugs especially the ones prescribed for chronic ailments. The sustained delivery of the drug would reduce the required frequency of administration which could extremely improve patient compliance and feeling of well-being. This study aimed to develop nanofibrous inserts for sustained ophthalmic delivery of timolol maleate (TIM) for the treatment of glaucoma. Experimental approach: Polycaprolactone-based nanofibers containing TIM were prepared using pure polycaprolactone or a blend of it with cellulose acetate or Eudragit RL100 polymers by the electrospinning method. Following the preparation, polymeric inserts were evaluated for morphological and physicochemical properties. The in vitro drug release was assessed and the in vivo efficacy of a selected insert in decreasing the intraocular pressure (IOP) was also evaluated in the equine eyes. Findings / Results: Prepared nanofibers indicated diameter ranged between 122-174 nm. The formulations showed suitable physicochemical properties and stability for ophthalmic administration. In vitro release study showed prolonged release of drug during more than 3 days. In vivo evaluation revealed that the prepared insert is non-irritant and non-toxic to the equine eyes while having suitable efficacy in decreasing the IOP during 6 days. Conclusions and implication: Prepared TIM inserts indicated a higher efficacy than commercial TIM eye drop in lowering IOP during a prolonged period. Thus, these formulations can be considered suitable for enhancing patient compliance by reducing the frequency of administration in the treatment of glaucoma.

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

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

Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and In Vitro Bioassay.

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.

Preparation and functional evaluation of electrospun polymeric nanofibers as a new system for sustained topical ocular delivery of itraconazole.

Due to the rapid clearance of external agents from the surface of the cornea, conventional ocular formulations usually require frequent and long duration of administration to achieve a therapeutic level of the drug on the cornea which can be conquered using prolonged-release nanofibrous inserts. In the present study, for the first time, polymeric nanofibers of itraconazole (ITZ), a potent triazole antifungal agent, were prepared as ocular inserts to enhance the topical ocular delivery of the drug. Three different nanofibers were prepared by electrospinning using polyvinyl alcohol-cellulose acetate and polycaprolactone-polyethylene glycol 12 000 polymeric blends. Nanofibers indicated uniform structures with the mean diameter ranging between 137 and 180 nm. Differential scanning calorimetry and Fourier-transform infrared spectroscopy confirmed the amorphous state of the drug in the formulations and the no drug-polymer interaction. Appropriate stability, suitable flexibility, and 2.2-3.9 MPa tensile strength were observed. Formulations indicated antifungal efficacy against Candida albicans and Aspergillus fumigatus and cell viability >70% at different concentrations. Results of bioassay against Candida albicans exhibited prolonged in vitro release of 50-70% of ITZ for almost 55 days. The results suggested that the nanofibers could be considered suitable for prolonged delivery of the ITZ as an antifungal requiring frequent and long duration of administration.

A Review on Ocular Novel Drug Delivery Systems of Antifungal Drugs: Functional Evaluation and Comparison of Conventional and Novel Dosage Forms.

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.