Zaghloul Nada, El Hoffy Nada M, Mahmoud Azza A, Elkasabgy Nermeen A
Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Future University in Egypt, Cairo 11835, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt.
Pharmaceutics. 2022 Feb 22;14(3):470. doi: 10.3390/pharmaceutics14030470.
This research assesses the beneficial effects of loading terconazole, a poorly water-soluble antifungal drug in silica/chitosan nanoparticles (SCNs) for ocular delivery. Nanoparticles were fabricated by the simple mixing of tetraethyl ortho silicate (TEOS) and chitosan HCl as sources of silica and nitrogen, respectively, along with alcoholic drug solution in different concentrations. Freeze-dried nanoparticles were fabricated using cyclodextrins as cryoprotectants. SCNs were assessed for their particle size, PDI, yield, drug loading and in vitro release studies. A 2.3 full factorial experimental design was constructed to optimize the prepared SCNs. DSC, XRD, FTIR, in addition to morphological scanning were performed on the optimized nanoparticles followed by an investigation of their pharmacokinetic parameters after topical ocular application in male Albino rabbits. The results reveal that increasing the water content in the preparations causes an increase in the yield and size of nanoparticles. On the other hand, increasing the TEOS content in the preparations, caused a decrease in the yield and size of nanoparticles. The optimized formulation possessed excellent mucoadhesive properties with potential safety concerning the investigated rabbit eye tissues. The higher C and AUC values coupled with a longer t value compared to the drug suspension in the rabbits' eyes indicated the potential of SCNs as promising ocular carriers for poorly water-soluble drugs, such as terconazole.
本研究评估了将水溶性差的抗真菌药物特康唑负载于用于眼部给药的二氧化硅/壳聚糖纳米颗粒（SCNs）中的有益效果。通过分别将原硅酸四乙酯（TEOS）和壳聚糖盐酸盐作为硅源和氮源，与不同浓度的含药醇溶液简单混合来制备纳米颗粒。使用环糊精作为冷冻保护剂制备冻干纳米颗粒。对SCNs进行粒径、多分散指数（PDI）、产率、载药量和体外释放研究。构建了2.3全因子实验设计以优化所制备的SCNs。对优化后的纳米颗粒进行差示扫描量热法（DSC）、X射线衍射（XRD）、傅里叶变换红外光谱（FTIR）以及形态扫描，随后在雄性白化兔局部眼部给药后研究其药代动力学参数。结果表明，制剂中含水量增加会导致纳米颗粒的产率和粒径增加。另一方面，制剂中TEOS含量增加会导致纳米颗粒的产率和粒径减小。优化后的制剂具有优异的粘膜粘附特性，对所研究的兔眼组织具有潜在安全性。与兔眼中的药物混悬液相比，更高的血药浓度（C）和药时曲线下面积（AUC）值以及更长的半衰期（t）表明SCNs作为水溶性差的药物（如特康唑）的有前景的眼部载体具有潜力。
