Alhakamy Nabil A, Hosny Khaled M, Rizg Waleed Y, Eshmawi Bayan A, Badr Moutaz Y, Safhi Awaji Y, Murshid Samar S A
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Gels. 2022 Apr 14;8(4):241. doi: 10.3390/gels8040241.
Fungal eye infections are largely disseminated, especially in developing countries where they may leave over half a million people blind per year. The current study aims to boost the voriconazole antifungal efficiency via loading it as cubosomes (VZ-Cub) into hyaluronic acid and poloxamer-based ocular in situ gel. VZ-Cub were fabricated applying Box-Behnken design and employing phytantriol, poloxamer F127, and VZ amounts as independent variables. The produced nano vesicles were evaluated for the dependent variables of particle size (PS), entrapment efficiency (EE%), and transcorneal steady-state flux (Jss) of the VZ, and, the obtained optimal VZ-Cub was loaded into an in situ gel base to enhance its ocular residence time. The in situ gel formulation was tested for its gelation temperature, drug release behavior, transcorneal permeation effects, and antifungal activity. The optimized VZ-Cub consisted of 100 mg of phytantriol, 60 mg of poloxamer F127, and 21 mg of VZ. This formulation led to a minimum PS of 71 nm, an EE% of 66%, Jss value of 6.5 µg/(cm·min), and stability index of 94 ± 2%. The optimized VZ-Cub-loaded in situ gel released 84% VZ after 12 h and yielded a 4.5-fold increase in drug permeation compared with the VZ aqueous dispersion. The antifungal activity, which was obtained by measuring the fungal growth inhibition zones, revealed that the VZ-Cub-loaded in situ gel formulation had a 3.89-fold increase in antifungal activity compared with the VZ dispersion. In summary, an ocular in situ gel loaded with VZ-Cub could be an effective novel nano-paradigm with enhanced transcorneal permeation and antifungal properties.
真菌性眼部感染在很大程度上具有传播性，尤其是在发展中国家，每年可能导致超过50万人失明。当前的研究旨在通过将伏立康唑（VZ）作为立方液晶纳米粒（VZ-Cub）负载到透明质酸和泊洛沙姆基眼用原位凝胶中来提高其抗真菌效率。采用Box-Behnken设计，以植烷三醇、泊洛沙姆F127和VZ的用量作为自变量来制备VZ-Cub。对制备的纳米囊泡进行了粒径（PS）、包封率（EE%）和VZ的角膜透过稳态通量（Jss）等因变量的评估，并将获得的最佳VZ-Cub负载到原位凝胶基质中以延长其眼部滞留时间。对原位凝胶制剂进行了胶凝温度、药物释放行为、角膜透过效果和抗真菌活性的测试。优化后的VZ-Cub由100 mg植烷三醇、60 mg泊洛沙姆F127和21 mg VZ组成。该制剂的最小PS为71 nm，EE%为66%，Jss值为6.5 μg/(cm·min)，稳定性指数为94±2%。优化后的负载VZ-Cub的原位凝胶在12小时后释放了84%的VZ，与VZ水分散体相比，药物渗透率提高了4.5倍。通过测量真菌生长抑制圈获得的抗真菌活性表明，负载VZ-Cub的原位凝胶制剂的抗真菌活性比VZ分散体提高了3.89倍。总之，负载VZ-Cub的眼用原位凝胶可能是一种有效的新型纳米范例，具有增强的角膜透过性和抗真菌特性。
