Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Drug Deliv. 2022 Dec;29(1):2945-2958. doi: 10.1080/10717544.2022.2120926.
The aim of this study was to formulate and boost ocular targeting of Fenticonazole Nitrate (FTN)-loaded olaminosomes in order to improve drug corneal permeation and candidiasis treatment. Olaminosomes were formulated by ethanol injection technique applying a central composite design. The independent variables were: span 80 amount (mg) (A), oleylamine concentration (mg%) (B) and oleic acid: drug ratio (C). The dependent responses were: percent entrapment efficiency (EE %), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and drug release after 10 hours (Q10h). Numerical optimization by Design-Expert® software was adopted to select the optimum formula. This formula was chosen based on highest EE %, ZP (as absolute value) and Q10h and lowest PS and PDI. The optimum formula was subjected to further characterization via Differential scanning calorimetry, Transmission electron microscopy, Fourier transform infrared spectroscopy, pH determination, effect of storage, influence of terminal sterilization, detection of Minimal Inhibitory Concentration and corneal penetration analysis. Safety and antifungal activity of the optimum formula were tested through various studies like ocular irritancy, corneal tolerance, corneal uptake and susceptibility test. The optimum formula with the maximum desirability value (0.972) revealed EE% (84.24%), PS (117.55 nm), ZP (-74.85 mV) and Q10h (91.26%) respectively. The optimum formula demonstrated ocular tolerance with enhanced corneal penetration behavior (428.66 µg/cm) and boosted antifungal activity (56.13%) compared to FTN suspension (174.66 µg/cm and 30.83%). The previous results ensured the ability of olaminosomes to enhance the corneal penetration and antifungal efficacy of Fenticonazole Nitrate.
本研究旨在将载有硝酸芬替康唑（FTN）的奥拉米诺体进行眼部靶向给药，以提高药物角膜渗透和念珠菌病治疗效果。奥拉米诺体采用乙醇注入技术，通过中心复合设计进行配方。自变量为：司盘 80 用量（mg）（A）、油胺浓度（mg%）（B）和油酸：药物比例（C）。因变量为：包封率（EE%）、粒径（PS）、多分散指数（PDI）、Zeta 电位（ZP）和 10 小时后的药物释放（Q10h）。采用 Design-Expert®软件进行数值优化，选择最佳配方。该配方基于最高 EE%、ZP（绝对值）和 Q10h，以及最低 PS 和 PDI 进行选择。对最佳配方进行进一步的差示扫描量热法、透射电子显微镜、傅里叶变换红外光谱、pH 值测定、贮藏影响、终端灭菌影响、最小抑菌浓度检测和角膜渗透分析。通过各种研究，如眼部刺激性、角膜耐受性、角膜摄取和敏感性试验，对最佳配方的安全性和抗真菌活性进行了测试。最佳配方的最大理想值（0.972）显示 EE%（84.24%）、PS（117.55nm）、ZP（-74.85mV）和 Q10h（91.26%）。与 FTN 混悬剂（174.66µg/cm 和 30.83%）相比，最佳配方表现出更好的角膜耐受性和增强的角膜穿透行为（428.66µg/cm 和 56.13%）。先前的结果证实了奥拉米诺体能够增强硝酸芬替康唑的角膜穿透和抗真菌效果。
