Antifungal evaluation of the association of terbinafine with potential antifungals encapsulated in nanostructured lipid carriers and incorporated in hydrogels against biofilms in onychomycosis models

• Grant number: 25/06625-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2025
• End date: August 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Maria José Soares Mendes Giannini
• Grantee: Bruna Almeida Furquim de Camargo
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 23/03556-1 - Study of the pathogenesis of mono/polymicrobial dermatophytes biofilms in ex vivo models and application of control strategies., AP.R

Abstract

Onychomycosis is one of the most prevalent fungal infections in the population, leading to various clinical manifestations in the nails. Among the pathogens, dermatophyte infection predominates, with Trichophyton rubrum being the most frequent species found, followed by the Trichophyton mentagrophytes complex. The infection affects the nail unit, causing thickening that makes it difficult to enter and administer topical medications. Oral and topical drug delivery systems are the most desirable in treating onychomycosis, but the efficacy of the results is low, resulting in a recurrence rate of 25-30%. Due to systemic toxicity and several other disadvantages associated with oral therapy, such as gastrointestinal and hepatotoxicity, topical therapy is commonly used, improving patient compliance and reducing the cost of treatment. Several advanced formulation approaches, such as transferosomes, liposomes, nano/microemulsion, nail polishes, etc., have been attempted to improve drug penetration into the nail plate more efficiently. However, due to poor nail plate penetration, current research has focused on chemical, mechanical, and physical methods to improve topical drug delivery. Furthermore, the microorganisms involved can form biofilms, a factor that hinders the action of antifungal agents. Thus, reports of antifungal resistance to oral treatments such as terbinafine and itraconazole drive the search for new therapeutic strategies. The present study aims to deepen the infection model and evaluate the antifungal action of the combination of terbinafine with potential antifungals encapsulated in nanostructured lipid carriers and incorporated in hydrogels against biofilm in vitro onychomycosis models with the dermatophytes T. rubrum and T. mentagrophytes and in vivo in Galleria mellonella. The comparative transcriptome of these models will be investigated to identify new therapeutic targets for treating dermatophytoses. (AU)