Formulações inovadoras de base nanotecnológica para o tratamento tópico de micoses superficiais

Abstract

Superficial mycoses are fungal diseases caused on skin, hair and nails and are among the infectious diseases with the highest incidence and difficult to treat, making them a serious public health problem. The purpose of this study was the development of nanotechnological based formulations, contemplating the use of vegetable lipids for topical application of tioconazole, aiming the treatment of superficial mycoses.The first part of this work was focused on the development of hydrogels containing Mangospheres (lipid nanoparticles prepared with mango butter, meleuca oil and tioconazole at 2 mg/mL), and hydrogels containing tioconazoleloaded copaiba oil polymeric nanocapsules, coated and uncoated with chitosan (1 mg/mL). Mangospheres were prepared by high-pressure homogenization technique and the polymeric nanocapsules by interfacial deposition of pre-formed polymer method. The nanoparticles showed adequate physicochemical characteristics. The mean particle size was around 100 nm for Mangospheres and 170 nm for copaiba oil nanocapsules. The formulations showed the polydispersity index below 0.15, slightly acid pH and negative zeta potential for Mangospheres and uncoated nanocapsules and positive for chitosan-coated nanocapasules. Tioconazole content was 1.64-1.74 mg/mL for Mangospheres and 1.00 mg/mL for copaiba nanocapsules. The formulations presented antifungal activity and a great control of tioconazole release was observed for Mangospheres containing melaleuca oil and for the uncoated nanocapsules. The nanostructures were preserved after incorporation into hydrogels. The hydrogels showed slightly acidic pH, drug content close to the theoretical values and flow characteristics in accordance with Casson model for hydrogels containing Mangopheres. The hydrogels containing the cationiccoated polymeric nanocapsules presented Hershel-Bulkley flow model and bioadhesivity. In vitro skin permeation studies showed tioconazole targeting to stratum corneum for the hydrogels presenting Mangospheres and copaiba oil nanocapsules, with greater retention for the hydrogels containing the coated copaiba oil nanocapsules. The second part of the present work focused on studies related to the optimization of formulations for the treatment of onychomycosis, starting with a review of the literature on the use of essential oils in treating these infections. In addition, it was aimed to develop a nail formulation containing tioconazole associated with nanocapsules of medium chain triglycerides coated with chitosan. The coated and uncoated nanocapsules were obtained by interfacial deposition of pre-formed polymer and showed nanometric size, adequate polydispersity index and positive zeta potential for the coated nanocapsules and negative for the uncoated particles. Tioconazole content was 1.00 mg/mL and pH with slightly acid values. Both formulations showed control of tioconazole release and antifungal activity. The nail formulation showed adequate characteristics for nail application and preserved the nanostructures while on nail permeation studies, presented higher percentage of tioconazole recovery from nail plate. Confocal microscopy analysis showed more than 30% of nail thickness in penetration depth of the fluorescent marker form the formulations. In an ex vivo onychomycosis model, the ungual formulations showed equivalent activity compared to the commercial tioconazole formulation with tioconazole concentration of 280 times lower. In addition, the association of tioconazole to polymeric nanocapsules led to a reduction of the irritative potential of the drug in vitro.