Terpinen-4-ol and nystatin co-loaded precursor of liquid crystalline system for topical treatment of oral candidiasis.

This study was performed to develop a liquid crystalline system (LCS) incorporated with terpinen-4-ol and nystatin to evaluate its antifungal, antibiofilm, and synergistic/modulatory activity against Candida albicans. The LCS was composed of a dispersion containing 40% propoxylated and ethoxylated cetyl alcohol, 40% oleic acid, and 0.5% chitosan dispersion. According to analysis by polarized light microscopy, rheology, and mucoadhesion studies, the incorporation of 100% artificial saliva increased the pseudoplasticity, consistency index, viscosity, and mucoadhesion of the formulation. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity; the LCS containing terpinen-4-ol and nystatin effectively inhibited C. albicans growth at a lower concentration, displaying a synergistic action. Therefore, LCS incorporated with terpinen-4-ol and nystatin is a promising alternative for preventing and treating infections and shows potential for the development of therapeutic strategies against candidiasis.

Antibiofilm efficacy of tea tree oil and of its main component terpinen-4-ol against Candida albicans.

Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - terpinen-4-ol - against resistant Candida albicans strains (genotypes A and B) identified by molecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell proliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of terpinen-4-ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and terpinen-4-ol present promising results for the treatment of oral candidiasis.

Antibiofilm efficacy of tea tree oil and of its main component terpinen-4-ol against Candida albicans

Abstract Candida infection is an important cause of morbidity and mortality in immunocompromised patients. The increase in its incidence has been associated with resistance to antimicrobial therapy and biofilm formation. The aim of this study was to evaluate the efficacy of tea tree oil (TTO) and its main component - terpinen-4-ol - against resistant Candida albicans strains (genotypes A and B) identified by molecular typing and against C. albicans ATCC 90028 and SC 5314 reference strains in planktonic and biofilm cultures. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity. Results were obtained from analysis of the biofilm using the cell proliferation assay 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and confocal laser scanning microscopy (CLSM). Terpinen-4-ol and TTO inhibited C. albicans growth. CLSM confirmed that 17.92 mg/mL of TTO and 8.86 mg/mL of terpinen-4-ol applied for 60 s (rinse simulation) interfered with biofilm formation. Hence, this in vitro study revealed that natural substances such as TTO and terpinen-4-ol present promising results for the treatment of oral candidiasis.

Antimicrobial effects of terpinen-4-ol against oral pathogens and its capacity for the modulation of gene expression.

This study evaluated the antibacterial activity of terpinen-4-ol against Streptococcus mutans and Lactobacillus acidophilus and its influence on gbpA (S. mutans) and slpA (L. acidophilus) gene expression. As measured by XTT assay, the concentrations of terpinen-4-ol that effectively inhibited the biofilm were 0.24% and 0.95% for S. mutans and L. acidophilus, respectively. Confocal microscopy revealed the presence of a biofilm attached to the enamel and dentin block surfaces with significant terpinen-4-ol effects against these microorganisms. The expression of the gbpA and slpA genes involved in adherence and biofilm formation was investigated using RT-PCR. Expression of these genes decreased after 15 min with 0.24% and 0.95% terpinen-4-ol in S. mutans and L. acidophilus, respectively. These findings demonstrate the antimicrobial activity of terpinen-4-ol and its ability to modulate the expression of gbpA and slpA genes, emphasizing the therapeutic capacity of terpinen-4-ol as an alternative to inhibit adherence in biofilm.

Efeito do óleo essencial de Melaleuca alternifolia e de seu principal componente Terpinen-4-ol sobre isolados clínicos de Candida albicans resistentes / Effect of Melaleuca alternifolia essential oil and its main component Terpinen-4-ol against clinical isolates of Candida albicans resistant

O óleo essencial de Melaleuca alternifolia (TTO) é um extrato de ação antifúngica e preventiva em escala farmacêutica ou cosmética. O objetivo deste estudo foi avaliar a eficácia do TTO e Terpinen-4-ol sobre isolados clínicos de Candida albicans. Este estudo foi realizado em três fases: 1- Identificação da CIM (Concentração Inibitória Mínima) e CFM (Concentração Fungicida Mínima) do TTO (0,25 a 2%) e Terpinen-4- ol (0,11 a 0,95%) sobre C. albicans na forma planctônica. 2- Análise das diferentes concentrações do óleo sobre biofilme monoespécie de C. albicans por meio da contagem das UFC/mL e avaliação da atividade metabólica das células pelo método colorimétrico de XTT. 3- Análise da ação inibitória das soluções de TTO e Terpinen-4- ol sobre biofilmes de C.albicans (cepa padrão e isolados clínicos) formados em corpos de prova de resina acrílica termopolimerizável previamente cobertos com saliva humana, por meio do teste de XTT e por microscopia confocal de varredura à laser (MCVL). A nistatina (Sigma) foi utilizada como controle positivo. Os resultados mostraram que isolados de C. albicans planctônicos foram sensíveis ao TTO 1%, Terpinen-4-ol 0,47% e Nistatina 8 ?g/mL. As menores concentrações fungicidas para os isolados foram TTO 2 %, Terpinen-4-ol 0,95 % e Nistatina 16 ?g/mL. Quando analisado em biofilme através da quantificação (UFC/mL) e teste de XTT as concentrações de TTO 2 % e Terpinen-4-ol 0,95 % foram eficazes quando comparado ao controle, sendo que as amostras da genotipagem A2 e B1 foram as mais resistentes. Os resultados de MCVL mostraram que todos os biofilmes desenvolvidos em corpos de resina acrílica apresentaram-se semelhantes à ação da Nistatina. Os extratos avaliados apresentaram ação antifúngica para os isolados clínicos e podem ser considerados tratamento alternativo para paciente com candidíase.

The essential oil of Melaleuca alternifolia (TTO) is an extract of antifungal action and preventive in pharmaceutical or cosmetic scale. The aim of this study was to evaluate the efficacy of TTO and Terpinen-4-ol against clinical isolates of Candida albicans. This study was conducted in three phases: 1- Identification of MIC (Minimum Inhibitory Concentration) and CFM (Minimum Fungicidal Concentration) of TTO (0.25 to 2%) and Terpinen-4-ol (0.11 to 0.95 %) on C. albicans in planktonic form . 2- Analysis of different concentrations of oil on C. albicans biofilm single species by counting CFU/mL and evaluation of the metabolic activity of cells by XTT colorimetric method. 3- Analysis of the inhibitory action of TTO and Terpinen-4-ol solutions on C. albicans biofilms (standard strain and clinical isolates) formed in specimens of polymerizable resin acrylic microwave previously coated with human saliva , by means of the XTT test and confocal laser scanning microscopy (CLSM) . The nystatin (Sigma) was used as a positive control. The results showed that isolates of C. albicans planktonic were sensitive to TTO 1%, Terpinen-4-ol 0.47% and Nystatin 8 mg/mL. The smaller fungicidal concentrations for the isolates were TTO 2%, Terpinen-4-ol 0.95% and Nystatin 16 mg / mL. When analyzed by quantifying biofilm (CFU / ml) and XTT test, the concentrations TTO 2% and Terpinen-4-ol 0.95% were effective when compared to the control, and genotyping of samples A2 and B1 were more resistant. The CLSM results showed that all biofilms developed in bodies of acrylic resin were similar to the action of Nystatin. The extracts showed antifungal action for the clinical isolates and can be considered an alternative treatment for patients with candidiasis