Topical hydrophilic gel with itraconazole-loaded polymeric nanomicelles improves wound healing in the treatment of feline sporotrichosis

Abstract

Sporotrichosis is a superficial fungal disease that can affect animals and humans. The high number of infected cats has been associated with zoonotic transmission and contributed to sporotrichosis being considered by the World Health Organization as one of the main neglected tropical fungal diseases for 2021–2030. Oral administration of itraconazole (ITZ) is the first choice for treatment, but it is expensive, time-consuming, and often related to serious adverse effects. As a strategy to optimize the treatment, we proposed the development of a hydrophilic gel with nanomicelles loaded with ITZ (HGN-ITZ). The HGN-ITZ was developed using an I-optimal design and characterized for particle size, Zeta potential, drug content, microscopic aspects, viscosity, spreadability, in vitro drug release, in vitro antifungal activity, and clinical evaluation in cats. The HGN-ITZ showed a high content of ITZ (97.3 ± 2.1 mg/g); and characteristics suitable for topical application (viscosity, spreadability, globules size, Zeta potential, controlled drug release). In a pilot clinical study, cats with disseminated sporotrichosis were treated with oral ITZ or HGN-ITZ + oral ITZ. A mortality rate of 21.3% was observed for the oral ITZ group compared to 5.3% for the HGN-ITZ + oral ITZ group. In a cat with a single lesion, topical treatment alone (HGN-ITZ) provided complete healing of the lesion in 45 days. No signs of topical irritation were observed during the treatments, suggesting that HGN-ITZ can be a promising strategy in the treatment of sporotrichosis.