الفهرس 
Title : A pharmaceutical study on using nanosystems for enhancing the delivery of a certain drug
ContentsOnly 14 pages are availabe for public view
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Abstract
Fungal keratitis is a serious corneal infection that can cause ocular damage and blindness if not treated effectively. Ocular trauma is considered the most common cause of fungal keratitis as it can introduce fungi directly into the cornea. Aspergillus spp. are among the most common causes of mycotic keratitis which, if not early diagnosed, can cause reduction in visual capacity due to its early macular involvement, choroidal damage and retinal necrosis. Topical antifungals which are formulated as conventional eye drops are considered as the optimal solution for fungal keratitis treatment due to their rapid onset of action, simplicity of instillation, low cost, noninvasiveness and better patient compliance. However, the efficacy of antifungal therapies through this route is limited by several physiological and anatomical barriers of the human eye; including blinking reflex which is responsible for the removal of about 95% of the applied dose, the tear film barrier, ocular surface small capacity, induced lacrimation, low corneal permeability and enzymatic degradation of the drugs by the anterior segment enzymes.
Tolnaftate (TOL) is a synthetic thiocarbamate antifungal agent acts selectively against filamentous fungi e.g., Aspergillus spp. Its fungicidal activity is mediated by inhibiting squalene epoxidase, an important microsomal enzyme in biosynthetic pathway of ergosterol (an essential component of the fungal membrane). Thus, squalene is accumulated in the cell wall of the fungi and ergosterol is depleted which affects membrane permeability and growth causing cell death. TOL is expected to be a promising candidate for the treatment of fungal keratitis due to its selective fungicidal properties, intermediate molecular mass (307.4) and lipophilicity (log P 5.5) which facilitate its penetration across the lipid rich epithelial and endothelial cell membrane. However, there is no satisfactory data inX
earlier literature about the use of TOL in an appropriate ocular delivery system for fungal keratitis treatment due to its poor water solubility (0.00054 mg/mL). The development of nanoformulations provides a new tool to overcome ocular barriers, improves drug retention time on the corneal surface and enhances drug permeability and bioavailability compared to conventional eye products.
Hence, designing novel ocular nanoparticulate carriers is hypothesized to enhance TOL aqueous solubility and consequently promote its ocular permeation and retention. Therefore, the goal of this thesis was to verify this hypothesis and attain the following specific aims:
1. Evaluate in details the joint effect of different formulation variables on the properties of different TOL nanosystems (polymeric pseudorotaxans, spanlastics and flexosomes).
2. Compare the ocular permeation potential of the prepared various TOL nanosystems for the purpose of investigating their potential in enhancing ocular TOL delivery.
3. Compare the in vitro antifungal activity of the prepared optimal TOL nanosystems.
4. Examine the tolerability and safety of the topically applied optimal TOL nanosystems by conducting in vivo histopathological studies.
5. Compare the drug’s retention capacity of the prepared optimal TOL nanosystems on the eye surface following topical administration by conducting in vivo susceptibility testing using Aspergillus niger.
Accordingly, the work in this thesis was divided into three main parts as follows:
Part I: Preparation and evaluation of tolnaftate polymeric pseudorotaxans.
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Part II: Preparation and evaluation of TOL elastic vesicles:
Chapter 1: Preparation and evaluation of tolnaftate spanlastics.
Chapter 2: Preparation and evaluation of tolnaftate flexosomes.
Part III: Ex vivo permeation, in vitro antifungal activity and in vivo studies of the selected nanosystems.