Pharmaceutical Nano-Technology Laboratory, Department of Medical Applications of Laser, National Institute of Laser Enhanced Sciences (NILES), Cairo University, Cairo, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
J Photochem Photobiol B. 2022 Jul;232:112461. doi: 10.1016/j.jphotobiol.2022.112461. Epub 2022 May 5.
Antimicrobial photodynamic inactivation (aPDI) has a tremendous potential as an alternative therapeutic modality to conventional antifungals in treatment of onychomycosis, yet the nail barrier properties and the deep-seated nature of fungi within the nails remain challenging. Therefore, the aim of this study was to prepare, optimize, and characterize Chorin e6 (Ce6) nail penetration enhancer containing vesicles (Ce6-nPEVs) and evaluate their photodynamic mediated effect against Trichophyton rubrum (T.rubrum); 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 was assessed in comparison with the free drug. The photodynamic treatment conditions for T.rubrum aPDI by free Ce6 was 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. 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.
抗菌光动力灭活（aPDI）作为一种替代传统抗真菌药物治疗甲真菌病的治疗方法具有巨大潜力，但指甲的屏障特性和真菌在指甲内的深层特性仍然具有挑战性。因此，本研究的目的是制备、优化和表征含有胞质素 e6（Ce6）的穿透增强型囊泡（Ce6-nPEVs），并评估其对红色毛癣菌（T.rubrum）的光动力介导作用；这是甲真菌病的主要致病因素。使用四因素两水平完全因子设计优化 nPEVs 的粒径和包封效率。与游离药物相比，评估了所选配方的透甲输送潜力。基于 Box-Behnken 设计的响应面法优化了游离 Ce6 对 T.rubrum aPDI 的光动力治疗条件，并在优化条件下评估了所选 Ce6-nPEVs 与游离 Ce6 的 aPDI 效果。结果表明，制剂对 Ce6 的包封效率高达 79.4%至 98%，粒径为 225nm 至 859nm，正 zeta 电位值为+30mV 至+70mV，粘度为 1.26cP 至 3.43cP。确定了使 Ce6-nPEVs 的包封效率最大化和粒径最小化的主要参数。与游离药物相比，所选配方的指甲水化程度提高了 1.8 倍，指甲摄取的 Ce6 百分比提高了 2.3 倍。微生物学研究结果证实了 Box-Behnken 模型的可靠性和充分性，并确定 Ce6 浓度和孵育时间为显著模型项。在优化条件下，游离 Ce6 和 Ce6-nPEVs 对 T.rubrum 表现出等效的体外杀菌作用，但 Ce6-nPEVs 预计在体内水平会表现出不同的效果，其中增强的指甲穿透特性的优势将得到证明。
