Ketoconazole-Loaded Cationic Nanoemulsion: In Vitro–Ex Vivo–In Vivo Evaluations to Control Cutaneous Fungal Infections

Abstract

An attempt has been made to optimize ketoconazole (KTZ)-loaded cationic nanoemulsion for topical delivery followed by in vitro , ex vivo , and in vivo evaluations. Central composite design suggested a total of 13 outcomes at 3 factors and 2 levels against 6 responses. Formulations were characterized for globular size, polydispersity index, pH, ζ potential, % entrapment efficiency (% EE), and drug content. Moreover, the optimized KTZ-CNM13 was compared against drug suspension (KTZ-SUS), commercial cream, and anionic nanoemulsion for in vitro drug release, ex vivo permeation, in vitro hemolysis, antifungal assay, in vivo dermal irritancy, and long-term stability. KTZ-CNM13 was found to have a low size (239 nm), an optimal ζ potential (+22.7 mV), a high % EE (89.1%), a spherical shape, a high drug content (98.9%), and a high numerical desirability value (1.0). In vitro drug release behavior of KTZ from KTZ-CNM13 was 7.54- and 1.71-folds higher than those of KTZ-ANM13 and KTZ-SUS, respectively, at 24 h. The permeation rate values were ordered as KTZ-CNM13 > KTZ-ANM13 > KTZ-MKT > KTZ-SUP due to various studied factors. High values of zone of inhibition for KTZ-CNM13 were observed against Candida albicans , Candida glabrata , Candida tropicalis, and Candida krusei as compared to KTZ-SUS. In vitro hemolysis and in vivo irritation studied confirmed the safety concern of the nanoemulsion at the explored composition. Long-term stability result revealed a stable product at the explored temperature for a year. Conclusively, cationic nanoemulsion is a promising approach to deliver KTZ for high permeation and therapeutic efficacy.

Natural Oils Enhance the Topical Delivery of Ketoconazole by Nanoemulgel for Fungal Infections

“…The authors reported a nanoemulsion size of 239 nm and the highest drug permeation of 95.34 ± 1.22 μg cm –2 . Furthermore, they noted a zone of inhibition of 44.2 ± 1.4 mm against the Candida krusei strain of fungi . The in vivo skin irritation study expressed that the in-house-developed formulation showed excellent tolerance to the skin due to biocompatibility.…”

“…The acute dermal irritation study previously reported by Shahid and associates is comparable to our skin irritation studies. 47 The work reported earlier on ketoconazole-loaded polylactic nanoparticles against C. albicans and other species reported only 45% encapsulation efficiency of ketoconazole, and the skin adhesiveness of the nanoparticles was not discussed in that work. 39 The luliconazole-loaded nanoemulgel was also prepared earlier for fungal infection.…”

“…Furthermore, they noted a zone of inhibition of 44.2 ± 1.4 mm against the Candida krusei strain of fungi. 47 The in vivo skin irritation study expressed that the in-house-developed formulation showed excellent tolerance to the skin due to biocompatibility. The acute dermal irritation study previously reported by Shahid and associates is comparable to our skin irritation studies.…”

“…The acute dermal irritation study previously reported by Shahid and associates is comparable to our skin irritation studies. 47 …”