ABSTRACT
The aim of this study was to evaluate the antifungal potential of 11 chloroacetamide derivatives and derivative incorporated into a film-forming system (FFS) as a potential alternative for the topical treatment of superficial and skin mycoses. The minimum inhibitory concentration (MIC) evaluation followed Clinical and Laboratory Standards Institute protocols M27-A3 (Candida) and M28-A2 (dermatophytes). Compounds 2, 3, and 4 were the most effective against Candida species (MIC range: 25-50 µg/mL) and dermatophytes (MIC range: 3.12-50 µg/mL). Compound 2 maintained its antifungal activity when incorporated in a FFS, with MIC values equivalent to the free compound. In addition, the compound does not act through complexation with ergosterol, suggesting that it may act on other targets of the fungal cell membrane. Chloroacetamide derivatives presented anti-Candida and anti-dermatophytic effectiveness. The FFS containing compound 2 has shown to be superior to traditional topical treatment of superficial and cutaneous fungal infections. It was found that these new chemical entities, with their applicability, are an excellent alternative to the topical treatment of fungal skin infections.
Subject(s)
Acetamides/therapeutic use , Arthrodermataceae/drug effects , Candida/drug effects , Dermatomycoses/drug therapy , Acetamides/administration & dosage , Acetamides/pharmacology , Administration, Topical , Antifungal Agents/therapeutic use , Dermatomycoses/microbiology , Humans , Microbial Sensitivity Tests , Skin/microbiologyABSTRACT
Fungal resistance is the major problem related to fluconazole treatments. This study aims to develop innovative lipid core nanocapsules and nanostructured lipid carriers containing fluconazole, to study in vitro antifungal activity and to assess the possibility of resistance reversion in Candida albicans, C. glabrata, C. krusei, and C. tropicalis isolates. The action mechanism of nanoparticles was investigated through efflux pumps and scanning electron microscopy studies. The lipid core nanocapsules and nanostructured lipid carriers were prepared by interfacial deposition of preformed polymer and high-pressure homogenization methods, respectively. Both nanostructures presented sizes below 250 nm, SPAN < 1.6, negative zeta potential, pH slightly acid, high drug content and controlled drug release. The nanostructured lipid carriers were unable to reverse the fungal resistance. Lipid core nanoparticles displayed advantages such as a reduction in the effective dose of fluconazole and resistance reversion in all isolates tested - with multiple mechanisms of resistance. The main role of the supramolecular structure and the composition of the nanoparticles on antifungal mechanisms of action were discussed. The results achieved through this study have an impact on clinical therapy, with a potential application in the treatment of fungal infections caused by resistant isolates of Candida spp.
Subject(s)
Antifungal Agents/pharmacology , Candida/drug effects , Delayed-Action Preparations/chemistry , Drug Resistance, Fungal/drug effects , Fluconazole/pharmacology , Fungal Proteins/antagonists & inhibitors , Nanoparticles/chemistry , ATP-Binding Cassette Transporters/antagonists & inhibitors , ATP-Binding Cassette Transporters/genetics , ATP-Binding Cassette Transporters/metabolism , Candida/genetics , Candida/growth & development , Candida/metabolism , Candida albicans/drug effects , Candida albicans/genetics , Candida albicans/growth & development , Candida albicans/metabolism , Candida glabrata/drug effects , Candida glabrata/genetics , Candida glabrata/growth & development , Candida glabrata/metabolism , Candida tropicalis/drug effects , Candida tropicalis/genetics , Candida tropicalis/growth & development , Candida tropicalis/metabolism , Caprylates/chemistry , Drug Compounding/methods , Drug Resistance, Fungal/genetics , Fungal Proteins/genetics , Fungal Proteins/metabolism , Gene Expression , Genes, MDR/drug effects , Hexoses/chemistry , Hydrogen-Ion Concentration , Microbial Sensitivity Tests , Nanoparticles/ultrastructure , Palmitates/chemistry , Particle Size , Triglycerides/chemistry , Verapamil/pharmacologyABSTRACT
This study focuses on the correlation investigation between rheological and physical parameters and how it can contribute to optimize the topical formulations development. A gel and an emulgel containing pinhão derivatives, and their respective controls, were analyzed along six months of storage. A flowchart of analyses was proposed to use in topical formulation development when a benchmark is the goal or when it is necessary to change some raw material. All formulations were stable over the storage time and the formulations containing pinhão starch and coat extract presented similar properties to those of the control formulations. Correlations between rheological and physical data, as moisture content and particle size, were determined using Pearson's correlation coefficient. A moderate positive correlation was verified between particle size distribution and flow index, and a strong positive correlation between particle size and flow index. It was also found that the higher the moisture content, the higher the consistency index, quality factor, and apparent viscosity. The correlation analyses applied in this study contributed to build up an analytical route for topical formulation development, saving time and costs.
