Abdollahi Diba, Jafariazar Zahra, Afshar Minoo
Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
J Cosmet Dermatol. 2020 Oct;19(10):2745-2751. doi: 10.1111/jocd.13317. Epub 2020 Feb 11.
Onychomycosis, a fungal nail infection, is an important problem as it may cause local pain, paresthesia, difficulties in performing activities of daily life, and impair social interactions. Systemic treatment of onychomycosis presents safety issues due to possible drug-drug interactions and severe side effects. Although topical therapy of onychomycosis is advantageous due to its localized effect, the efficacy of such therapy depends on achieving effective concentrations of antifungal agents at the infection site. An approach to reach to this end would be driving benefit from synergic activity of antifungal agents for example itraconazole and monoterpenes. However, because of low transungual penetration of itraconazole, a molecule with high molecular weight and very low water-solubility, the effect of the latter compounds on itraconazole nail delivery should be investigated, which was the aim of this study.
Ex vivo permeation experiments were carried out through soaking the nail clippings of ten healthy volunteers in control and working solutions containing itraconazole (1 mg mL ) and itraconazole (1 mg mL ) plus 6% of each monoterpene including camphor, eucalyptol, menthol, and thymol, respectively, for 36 hours. The amount of itraconazole in nail clippings was quantified hereafter using a validated HPLC method.
Statistical analysis showed that itraconazole transungual permeation was not influenced by the studied monoterpenes (P value > .05).
These results provided a new perspective for designing topical dosage forms for the treatment of onychomycosis.
甲癣是一种指甲真菌感染，是一个重要问题，因为它可能导致局部疼痛、感觉异常、日常生活活动困难并损害社交互动。由于可能存在药物相互作用和严重副作用，甲癣的全身治疗存在安全问题。虽然甲癣的局部治疗因其局部作用而具有优势，但其疗效取决于在感染部位达到抗真菌剂的有效浓度。实现这一目标的一种方法是利用抗真菌剂（如伊曲康唑和单萜类化合物）的协同活性。然而，由于伊曲康唑分子量高且水溶性极低，经指甲渗透能力低，因此应研究后一类化合物对伊曲康唑经指甲递送的影响，这就是本研究的目的。
通过将10名健康志愿者的指甲剪浸泡在分别含有伊曲康唑（1mg/mL）以及伊曲康唑（1mg/mL）加6%的每种单萜类化合物（包括樟脑、桉叶油醇、薄荷醇和百里香酚）的对照溶液和工作溶液中36小时，进行体外渗透实验。此后，使用经过验证的高效液相色谱法对指甲剪中的伊曲康唑含量进行定量。
统计分析表明，伊曲康唑经指甲渗透不受所研究的单萜类化合物影响（P值>.05）。
这些结果为设计治疗甲癣的局部剂型提供了新的视角。
