Department of Pharmaceutics, Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA) - CONICET, Córdoba, Argentina.
Eur J Pharm Biopharm. 2020 Sep;154:50-61. doi: 10.1016/j.ejpb.2020.06.025. Epub 2020 Jul 8.
The administration of conventional dosage forms of itraconazole (ITZ) for cutaneous candidiasis treatment is limited by its poor aqueous solubility and the deep location ofCandida albicans(CA) in this disease. In the present work, we developed a nanocrystal (NC) form of ITZ, which was incorporated into dissolving microneedles (MNs) to facilitate skin delivery of ITZ into the infection site. The NCs were prepared by media milling with an ultra-small-scale device using Pluronic®F127 as a stabiliser. The antifungal activity of ITZ was enhanced by NC formulations (MIC value of 2.5 μg/ml), compared to a coarse dispersion of ITZ (MIC value of >2560 μg/ml). The formulation of ITZ into NCs increased dissolution rate by 3-fold. Furthermore, the dissolving MNs containing ITZ-NCs exhibited better dermatokinetic profiles, compared to needle-free patches and conventional creams containing ITZ-NCs. Importantly, the antifungal activity in anex vivocandidiasis infection model exhibited that the CA viability declined by up to 100% after 48 h of administration. These studies have verified the concept that the incorporation of ITZ-NCs into dissolving MNs can offer an effective approach for cutaneous candidiasis treatment.
伊曲康唑（ITZ）的常规剂型用于治疗皮肤念珠菌病的应用受到其较差的水溶性和这种疾病中白色念珠菌（CA）在深层位置的限制。在本工作中，我们开发了一种 ITZ 的纳米晶体（NC）形式，将其纳入溶解微针（MN）中，以促进 ITZ 递送至感染部位的皮肤。NC 是通过使用 Pluronic®F127 作为稳定剂的超小型设备中的介质研磨制备的。与 ITZ 的粗分散体（MIC 值>2560μg/ml）相比，NC 制剂增强了 ITZ 的抗真菌活性（MIC 值为 2.5μg/ml）。NC 制剂将 ITZ 配方的溶解速率提高了 3 倍。此外，与含有 ITZ-NC 的无针贴片和常规乳膏相比，含有 ITZ-NC 的溶解 MN 表现出更好的皮肤动力学特征。重要的是，在体外念珠菌感染模型中的抗真菌活性研究表明，给药 48 小时后 CA 的存活率下降了高达 100%。这些研究验证了将 ITZ-NC 纳入溶解 MN 中可以为皮肤念珠菌病治疗提供有效方法的概念。
