Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Int J Nanomedicine. 2020 Oct 12;15:7825-7840. doi: 10.2147/IJN.S268208. eCollection 2020.
Voriconazole (VRC) is a triazole broad spectrum antifungal drug, used in the management of versatile fungal infections, particularly fungal keratitis. The obligatory use of niosomal delivery of VRC may reduce the frequency of dosing intervals resulting from its short biological half time and consequently improve patient compliance.
VRC loaded proniosomes (VRC-PNs) were set by the coacervation technique and completely characterized. The developed formula was comprehensively assessed concerning in- vitro release behavior, kinetic investigation, and its conflict against refrigerated and room temperature conditions. A selected noisomal formula was incorporated into ocusert (VRC-PNs Ocu) formulated by 1% w/w hydroxypropyl methyl cellulose HPMC and 0.1% w/w carbopol . Eventually, in vitro antifungal activity against and was assessed by the cup diffusion method.
The optimized VRC-PNs (Pluronic F127: cholesterol weight ratio 1:1 w/w) exhibited the highest entrapment efficiency (87.4±2.55%) with a spherical shape, proper size in nano range and a suitable Zeta potential of 209.7±8.13 nm and -33.5±1.85 mV, respectively. Assurance of drug encapsulation in nanovesicles was accomplished by several means such as attenuated total reflection Fourier-transform infrared spectroscopy, differential scanning calorimetry in addition to powder X-ray diffraction investigations. It displayed a biphasic in vitro release pattern and after 6 months of storage at a refrigerated temperature, the optimized formula preserved its stability. VRC-PNs Ocu proved a very highly significant antifungal activity matched with the free drug or nanosuspension which was extra assured by comparing its mean inhibition zone with that of 5% natamycin market eye drops.
In conclusion, VRC-PNs Ocu could be considered as a promising stable sustained release topical ocular nanoparticulate system for the management of fungal infections.
伏立康唑（VRC）是一种三唑类广谱抗真菌药物，用于治疗多种真菌感染，特别是真菌性角膜炎。使用非离子型脂质体递药可能会减少由于其半衰期短而导致的给药间隔频率，从而提高患者的依从性。
采用凝聚法制备伏立康唑前体脂质体（VRC-PNs），并对其进行全面表征。对所开发的配方进行了体外释放行为、动力学研究以及对冷藏和室温条件的稳定性考察。选择一种合适的非离子型脂质体配方，与 1%w/w羟丙基甲基纤维素（HPMC）和 0.1%w/w卡波姆制成 Ocusert（VRC-PNs Ocu）。最后，采用杯碟扩散法评估其对 和 的体外抗真菌活性。
优化的 VRC-PNs（Pluronic F127：胆固醇重量比为 1:1w/w）具有最高的包封效率（87.4±2.55%），呈球形，纳米级大小合适，Zeta 电位为 209.7±8.13nm，-33.5±1.85mV。采用衰减全反射傅里叶变换红外光谱、差示扫描量热法和粉末 X 射线衍射研究等多种方法证实了药物包封在纳米囊泡中。体外释放呈双相模式，在冷藏温度下储存 6 个月后，优化配方保持稳定。VRC-PNs Ocu 显示出非常高的抗真菌活性，与游离药物或纳米混悬剂相当，通过比较其平均抑菌圈与 5%那他霉素市售眼药水的抑菌圈，进一步证实了这一点。
总之，VRC-PNs Ocu 可以被认为是一种有前途的稳定的真菌性角膜炎局部缓释纳米给药系统。
