Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of Pharmacy, Universidade Federal de Goiás (UFG), Rua 240, esq. com 5ª Avenida, Setor Leste Universitário, 74605-170 Goiânia, GO, Brazil.
Physics Department, Universidade Federal de Catalão (UFCAT), Catalão, GO, Brazil.
Int J Pharm. 2021 Jun 1;602:120597. doi: 10.1016/j.ijpharm.2021.120597. Epub 2021 Apr 20.
This work aimed to select an effective penetration enhancer (PE) for nail pretreatment, develop voriconazole (VOR)-loaded nanomicelles, and evaluate their ability to deliver VOR to the nail. A complete analysis of nail protein dynamics, bond rupture, and microstructure was performed. Alternative methods as electron paramagnetic resonance (EPR) and the Ellman's reagent (DTNB) assay were also evaluated. Nanomicelles were produced and characterized. The PE hydrated the hooves, following the order: urea ≈ cysteine ≈ glycolic acid < thioglycolic acid (TGA) < NaOH. SEM images and methylene blue assay showed enlarged pores and roughness of porcine hooves after incubation with NaOH and TGA. EPR was demonstrated to be the most sensitive technique. DTNB assay quantified higher thiol groups for samples treated with TGA (p < 0.05). A stratigraphic analysis with Raman spectroscopy demonstrated that hooves treated with TGA presented a higher SH/SS ratio at the edges, affecting protein secondary structure. In vitro permeation studies demonstrated significant VOR permeation (29.44 ± 6.13 µg/cm), 10-fold higher than previous studies with lipid nanoparticles. After TGA pretreatment, VOR permeation was further enhanced (3-fold). TGA pretreatment followed by VOR-loaded nanomicelles demonstrates a promising approach for onychomycosis treatment. The novel methods for protein analysis were straightforward and helpful.
本工作旨在选择一种有效的透皮促进剂（PE）用于指甲预处理，制备伏立康唑（VOR）载纳米胶束，并评估其向指甲递送 VOR 的能力。对指甲蛋白动力学、键断裂和微观结构进行了全面分析。还评估了替代方法，如电子顺磁共振（EPR）和 Ellman 试剂（DTNB）测定法。制备并表征了纳米胶束。PE 使蹄水化，顺序为：尿素≈半胱氨酸≈乙醇酸<巯基乙酸（TGA）<氢氧化钠。SEM 图像和亚甲蓝试验表明，用 NaOH 和 TGA 孵育后，猪蹄的孔增大且变粗糙。EPR 被证明是最敏感的技术。DTNB 测定法表明，用 TGA 处理的样品中巯基基团数量更多（p<0.05）。拉曼光谱的分层分析表明，用 TGA 处理的蹄在边缘处呈现出更高的 SH/SS 比，影响蛋白质二级结构。体外渗透研究表明 VOR 渗透显著（29.44±6.13µg/cm），比以前用脂质纳米粒进行的研究高 10 倍。TGA 预处理后，VOR 渗透进一步增强（增加 3 倍）。TGA 预处理后负载 VOR 的纳米胶束显示出一种有前途的治疗甲真菌病的方法。用于蛋白质分析的新方法简单直接且有帮助。
