الفهرس 
Title pageOnly 14 pages are availabe for public view
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Abstract
Limited success rate and rising resistance to conventional antifungals used for the treatment of onychomycosis creates a need for new therapeutic approaches. Antimicrobial photodynamic inactivation (aPDI) has a tremendous potential as an alternative therapeutic modality, yet the nail barrier properties and the deep-seated nature of fungi within the nails remain challenging. The integration between aPDI and nanotechnology could overcome such a problem, therefore, the aim of this study was to prepare, optimize, and characterize Chorine e6 (Ce6) nail penetration enhancer containing vesicles (Ce6-nPEVs) and evaluate their photodynamic mediated effect against Trichophyton rubrum (T.rubrum), which is the main causative agent of onychomycosis. Optimization of the particle size and encapsulation efficiency of nPEVs was performed using a four-factor two-level full factorial design. The transungual delivery potential of the selected formulation in terms of nail hydration and transungual drug uptake was assessed in comparison with the free drug. The photodynamic treatment conditions for T.rubrum aPDI by free Ce6 were optimized using response surface methodology based on Box–Behnken design, and the aPDI effect of the selected Ce6-nPEVs was evaluated versus the free Ce6 at the optimized condition. The effectiveness and safety of PDT mediated by Ce6-nPEVs were evaluated on an onychomycotic patient as a case study. Results showed that formulations exhibited high encapsulation efficiency for Ce6 ranging from 79.4 to 98%, particle sizes ranging from 225 to 859 nm, positive zeta potential values ranging from +30 to +70 mV, and viscosity ranging from 1.26 to 3.43 cP. The predominant parameters for maximizing the encapsulation efficiency and minimizing the particle size of Ce6-nPEVs were identified. The selected formulation showed 1.8-folds higher nail hydration and 2.3 folds improvement in percentage of Ce6 up-taken by nails compared to the free drug. Results of the microbiological study confirmed the reliability and adequacy of the Box–Behnken model, and delineated Ce6 concentration and incubation time as the significant model terms. Free Ce6 and Ce6-nPEVs showed an equipotent in vitro fungicidal effect on T.rubrum at the optimized conditions, however Ce6-nPEVs is expected to show a differential effect at the in vivo level where the advantage of the enhanced nail penetration feature will be demonstrated. The patient treated with Ce6nPEVs-PDT achieved complete healing after 9 sessions with 2 weeks interval in between. No pain or side effects were reported neither during the irradiation nor later, clinical cure persisteduntil the end of a follow up period of 5 months after the last session.