Aziz Diana, Mohamed Sally A, Tayel Saadia, Makhlouf Amal
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 12613, Egypt.
Pharmaceutics. 2022 Aug 22;14(8):1746. doi: 10.3390/pharmaceutics14081746.
Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 3 factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 3.2 factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of -32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery.
托萘酯（TOL）是一种硫代氨基甲酸盐类杀真菌药物，以乳膏和软膏的形式局部使用。由于其水溶性差以及独特的眼部屏障，目前尚无用于治疗真菌性角膜炎（FK）的托萘酯眼部制剂。因此，本研究旨在通过使用不同二醇调节弹性体组成来开发新型改性弹性体，以增强托萘酯的眼部给药效果。为实现这一目标，采用全3因素设计，通过乙醇注入法制备了托萘酯基础弹性体。通过应用期望函数，选择了最佳配方（BS6），并将其作为核心，根据全3.2因素设计制备和优化托萘酯-助溶剂弹性体。使用30%丙二醇制备了最佳配方（MS6），其包封率（EE%）为66.10±0.57%，粒径（PS）为231.20±0.141nm，ζ电位（ZP）为-32.15±0.07mV。将MS6与BS6进行比较，两种纳米囊泡均比药物混悬液显著提高了托萘酯的角膜渗透潜力。此外，还完成了体内组织病理学实验，证实了MS6在眼部使用的耐受性。使用……进行的真菌药敏试验证实，MS6比药物混悬液表现出更持久的生长抑制作用。因此，MS6可能是增强托萘酯眼部给药的一个有前景的选择。
