Mady Omar Y, Al-Madboly Lamiaa A, Donia Ahmed A
Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.
Front Microbiol. 2020 Apr 3;11:385. doi: 10.3389/fmicb.2020.00385. eCollection 2020.
Cutaneous mycoses, particularly tinea pedis caused by , are commonly known infections in humans. They are still considered as a major public health problem worldwide affecting the quality of life due to prolonged period of treatment and development of drug resistance, which leads to recurrence of infections. The objective of our study was to assess the effectiveness of miconazole in the presence and absence of urea, as a penetration enhancer, against and to formulate both of them in a water-soluble film to be applied topically for the purpose of treating tinea pedis caused by this fungus. Drug combination revealed synergism where miconazole minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) (0.5 and 1 mg/L) were considerably declined to 0.001 and 0.004 mg/L, respectively, when combined with 20% urea. This enhanced drug interaction activity against the test strain was explained by the alterations raised on the morphology and ultrastructures observed microscopically. Minimal fungicidal dose of miconazole/urea combination displayed plasmolysis and shrink cytoplasm; however, necrotic cells with punctured walls and degraded cytoplasmic content were observed at high fungicidal dose. Water-soluble films, prepared using increasing values of miconazole MFC and urea, were transparent, smooth, uniform, and flexible. Their physicochemical characters showed homogeneity in weight, thickness, drug content, and folding endurances with normal surface pH values, indicating the reproducibility of the preparation method. The novel simulation model for the film mechanism of action supported the idea and the suggested application method of the new dosage form. Evaluation of these films was carried using disk diffusion assay as well as using guinea pig dermatophytosis model. The assessment revealed an increase in the inhibition zone diameters in a concentration-dependent manner upon using 10 or 20% of urea combined with miconazole. test showed that combination of 0.004 mg/L miconazole with 20% urea (M + U20) showed the highest efficacy percentage (95.83%), which was statistically superior to the infected untreated control ( < 0.001) in fungal burden reduction as well as improvement in clinical scores ( < 0.001). This work supports the hypothesis and suggests a new promising dosage form for the treatment of infections.
皮肤癣菌病，尤其是由[具体真菌名称未给出]引起的足癣，是人类常见的感染病。由于治疗周期长以及耐药性的产生导致感染复发，它们在全球范围内仍被视为影响生活质量的主要公共卫生问题。我们研究的目的是评估咪康唑在有和没有作为渗透促进剂的尿素存在的情况下对[具体真菌名称未给出]的有效性，并将它们制成水溶性薄膜用于局部治疗由这种真菌引起的足癣。药物组合显示出协同作用，当与20%尿素联合使用时，咪康唑的最小抑菌浓度（MIC）和最小杀菌浓度（MFC）（分别为0.5和1mg/L）大幅降至0.001和0.004mg/L。通过显微镜观察到的形态和超微结构的改变解释了这种增强的针对测试菌株的药物相互作用活性。咪康唑/尿素组合的最小杀菌剂量显示出质壁分离和细胞质收缩；然而，在高杀菌剂量下观察到细胞壁穿孔和细胞质内容物降解的坏死细胞。使用增加的咪康唑MFC和尿素值制备的水溶性薄膜是透明、光滑、均匀且柔韧的。它们的物理化学特性在重量、厚度、药物含量和折叠耐久性方面表现出均匀性，表面pH值正常，表明制备方法具有可重复性。薄膜作用机制的新型模拟模型支持了新剂型的理念和建议的应用方法。使用纸片扩散法以及使用豚鼠皮肤癣菌病模型对这些薄膜进行了评估。纸片扩散法评估显示，当使用10%或20%的尿素与咪康唑联合使用时，抑菌圈直径呈浓度依赖性增加。豚鼠试验表明，0.004mg/L咪康唑与20%尿素的组合（M + U20）显示出最高的疗效百分比（95.83%），在减轻真菌负荷以及改善临床评分方面在统计学上优于未治疗的感染对照（P < 0.001）。这项工作支持了该假设，并为治疗[具体真菌名称未给出]感染提出了一种新的有前景的剂型。
