الفهرس 
SummaryOnly 14 pages are availabe for public view
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Abstract
Background: Conventional dosage forms suffer from the problem of poor ocular bioavailability due to various dominant anatomical and pathophysiological barriers in the eye. The application of nanotechnology in medical fields is experiencing rapid progress to overcome some drawbacks associated with ophthalmological drugs. In this study, voriconazole and mizolastine were chosen as two drug models that possess problematic characters in ophthalmic application. Objectives: The aim of the first part of this study was to investigate the potential use of voriconazole proniosomal gels (VRC-PNs) and to investigate the antiallergic activity of MZL-SLNs formulations in the second part. Methods: Preparation of voriconazole as proniosomes employing cholesterol in various ratios relative to different surfactants. Determination of particle size, polydispersity index, Zeta potential and entrapment efficiency for the developed proniosomes. Further characterization of the optimized formula using (FTIR), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) as well as the in-vitro release profiles at pH value 7.4 was also performed. Incorporation of the optimized formulation into ocular inserts. Microbiological study by means of cup diffusion method and measurements of mean diameter of inhibition zone was also performed. Preparation of MZL-SLNs formulations using different quantities of glyceryl monostearate (GMS) as a lipid and tween 80 as a stabilizer. Evaluation of the formed SLNs with respect to their particle size, PDI, Zeta potential and entrapment efficiency. Further characterization of the optimum formula using FTIR, PXRD, DSC, SEM and TEM. Incorporation of the optimized formulation into hydrogels. Investigation of the anti-allergic activity of MZL-SLNs loaded hydrogels by assessment of histopathological examination after topical application to albino rabbits in comparison with free drug loaded hydrogel. Results: Physiochemical evaluation of VRC-niosomal ocuserts shows that, the average weight of 100±20 mg, drug content of 98.2±1.1% as well as pH 6.8±0.3 are optimum for ocular delivery. In-vitro drug release indicated that, the diffusion of the drug was prolonged by the optimized proniosomes as well as its VRC-niosomal ocuserts. Progressed VRC-loaded noisomal suspension (F7) displays more stability at refrigerated temperature. VRC-PNs ocuserts containing voriconazole in a concentration of 1 % w/w have significant higher inhibition zone compared to the reference natamycin eye drops. Solid state characterization confirmed that MZL well encapsulated in SLNs as well as the drug was in an amorphous state. TEM and SEM images indicated the formation of spherical particles in nano-size range. In-vitro release studies showed a sustained release from F4-hydrogel up to 36 h, and following non-Fickian Higuchi kinetics model at pH 6.8. pretreatment with MZL-SLNs loaded hydrogel imparted a reversal of the abnormal regulation of inflammation as well as marked decreased tissue necrosis factor-α (TNF-α) and vascular endothelium growth factor (VEGF) expression levels, in rabbits with non-infectious conjunctivitis in comparison to post-treatment with the same formula.
Conclusion: finally, we concluded that, VRC-PNs ocuserts deserve a deep consideration for their potential future application as a hopeful nanoparticulate system for severe ocular antifungal infections. Also, we confirmed the desirable potential of solid lipid nanoparticles for ocular delivery of mizolastine with enhancement of the antiallergic activity in rabbits’ eyes model.