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作者：Andi Dian Permana^a; Alejandro J.Paredes^bc; Fabiana Volpe-Zanutto^b; Qonita Kurnia Anjani^b; Emilia Utomo^b; Ryan F.Donnelly^b 

^aDepartment of Pharmaceutics, Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia

^bSchool of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK

^cUnidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA) – CONICET, Córdoba, Argentina

摘要：The administration of conventional dosage forms of itraconazole (ITZ) for cutaneous candidiasis treatment is limited by its poor aqueous solubility and the deep location of Candida 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 an ex vivo candidiasis 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.