Porosity of temporary denture soft liners containing antifungal agents

ABSTRACT Incorporation of antifungals in temporary denture soft liners has been recommended for denture stomatitis treatment; however, it may affect their properties. Objective: To evaluate the porosity of a tissue conditioner (Softone) and a temporary resilient liner (Trusoft) modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm. Material and Methods: The porosity was measured by water absorption, based on exclusion of the plasticizer effect. Initially, it was determined by sorption isotherms that the adequate storage solution for specimens (65×10×3.3 mm) of both materials was 50% anhydrous calcium chloride (S50). Then, the porosity factor (PF) was calculated for the study groups (n=10) formed by specimens without (control) or with drug incorporation at MICs (nystatin: Ny-0.032 g, chlorhexidine diacetate: Chx-0.064 g, or ketoconazole: Ke-0.128 g each per gram of soft liner powder) after storage in distilled water or S50 for 24 h, seven and 14 d. Data were statistically analyzed by 4-way repeated measures ANOVA and Tukey's test (α=.05). Results: Ke resulted in no significant changes in PF for both liners in water over 14 days (p>0.05). Compared with the controls, Softone and Trusoft PFs were increased at 14-day water immersion only after addition of Ny and Chx, and Chx, respectively (p<0.05). Both materials showed no significant changes in PF in up to 14 days of S50 immersion, compared with the controls (p>0.05). In all experimental conditions, Softone and Trusoft PFs were significantly lower when immersed in S50 compared with distilled water (p<0.05). Conclusions: The addition of antifungals at MICs resulted in no harmful effects for the porosity of both temporary soft liners in different periods of water immersion, except for Chx and Ny in Softone and Chx in Trusoft at 14 days. No deleterious effect was observed for the porosity of both soft liners modified by the drugs at MICs over 14 days of S50 immersion.

Efeito da incorporação de agentes antifúngicos na resistência à tração e porosidade de materiais resilientes temporários para base de próteses / Effect of incorporation of antifungal agents on the ultimate tensile strength and porosity of temporary soft denture liners

Este estudo investigou a resistência à tração (ou limite de resistência à tração- LRT) e a porosidade de reembasadores resilientes temporários modificados por concentrações inibitórias mínimas (CIMs) de agentes antifúngicos para o biofilme Candida albicans (SC5314). Para os testes de LRT, corpos de prova em forma de halteres (n=7) com uma área transversal de 33 mm x 6 mm x 3 mm foram produzidos para os materiais resilientes (Trusoft e Softone) sem (controle) ou com incorporação de cinco fármacos em suas CIMs: nistatina- 0,032 g; diacetato de clorexidina- 0,064; cetoconazol- 0,128 g; miconazol- 0,256 g; itraconazol-0,256 g (grama de fármaco por grama de pó de material resiliente). Após a plastificação, as amostras foram imersas em água destilada a 37°C durante 24 h, 7 e 14 dias e, então, testadas em tensão em uma máquina universal de ensaios (EMIC DL-500 MF) a 40 mm/min. A porosidade foi mensurada por absorção de água, com base na exclusão do efeito plastificante. Inicialmente, determinou-se por isotermas de sorção, que a solução de armazenagem adequada para os corpos de prova (65 mm x 10 mm x 3,3 mm) de ambos os materiais foi o cloreto de cálcio anidro a 50% (S50). Assim, o fator de porosidade (FP) foi calculado para os grupos de estudo (n=10) formados por espécimes sem (controle) ou com incorporação de fármaco em suas CIMs (nistatina, clorexidina ou cetoconazol) após a armazenagem em água destilada ou S50 por 24 h, 7 e 14 dias. Os dados de resistência à tração (MPa) e percentagem de alongamento (%) foram submetidos à ANOVA de 3 fatores seguida pelo teste de Tukey (=0,05). Os dados de porosidade foram analisados estatisticamente por ANOVA de medidas repetidas para 4 fatores e teste de Tukey (=0,05). Ao final de 14 dias, a resistência à tração para ambos os materiais foi significativamente menor nos grupos modificados pelo miconazol e itraconazol em relação aos outros grupos (P<0,0001), que não mostraram diferenças significativas entre si (P>0,05). Após 7 e 14 dias em água, o miconazol e itraconazol adicionados a ambos os materiais resultaram em percentagens significativamente menores de alongamento em comparação com os outros fármacos e ao controle (P<0,0001), que foram semelhantes entre si (P>0,05). O cetoconazol não resultou em alterações significativas no FP para ambos os materiais resilientes em água ao longo de 14 dias (P>0,05). Em comparação aos controles, houve aumento dos FPs do Softone e Trusoft aos 14 dias de imersão em água somente após a adição de nistatina e clorexidina e de clorexidina, respectivamente (P<0,05). Ambos os materiais não apresentaram alterações significativas no FP em até 14 dias de imersão na S50, em comparação aos controles (P>0,05). Em todas as condições experimentais, os FPs do Softone e Trusoft foram significativamente menores quando imersos em S50 em comparação com a água destilada (P<0,05). Concluiu-se que a adição de nistatina, clorexidina e cetoconazol nas CIMs para o biofilme de C. albicans não resultou em efeitos deletérios na resistência à tração e na percentagem de alongamento dos materiais resilientes temporários para base de prótese até o período de 14 dias. A adição de antifúngicos nas CIMs não resultou em efeitos adversos à porosidade de ambos os materiais resilientes temporários em diferentes períodos de imersão em água, com exceção da clorexidina e nistatina no Softone e clorexidina no Trusoft aos 14 dias. Não foram observados efeitos deletérios para a porosidade de ambos os materiais resilientes modificados com as CIMs dos fármacos durante os 14 dias de imersão na S50.(AU)

This study investigated the tensile strength (ultimate tensile strength- UTS) and porosity of temporary soft denture liners modified by minimum inhibitory concentrations (MICs) of antifungal agents for Candida albicans biofilm (SC5314). For UTS tests, dumbbell-shaped specimens (n=7) with a central cross-sectional area of 33 mm x 6 mm x 3 mm were produced by resilient materials (Trusoft and Softone) without (control) or with incorporation of five drugs at MICs: nystatin- 0.032 g; chlorhexidine diacetate-0.064 g; ketoconazole- 0.128 g; miconazole- 0.256 g; itraconazole- 0.256 g (each per gram of soft liner powder). After plasticization, specimens were immersed in distilled water at 37°C for 24 h, 7 and 14 days, and then tested in tension in a universal testing machine (EMIC DL-500 MF) at 40 mm/min. The porosity was measured by water absorption, based on exclusion of the plasticizer effect. Initially, it was determined by sorption isotherms that the adequate storage solution for specimens (65 mm x 10 mm x 3.3 mm) of both materials was 50% anhydrous calcium chloride (S50). Then, the porosity factor (PF) was calculated for the study groups (n=10) formed by specimens without (control) or with drug incorporation at MICs (nystatin, chlorhexidine or ketoconazole) after storage in distilled water or S50 for 24 h, 7 and 14 days. Data of tensile strength (MPa) and elongation percentage (%) were submitted to 3-way ANOVA followed by Tukey's test (=0.05). Data of porosity were statistically analyzed by 4-way repeated measures ANOVA and Tukeys test (=0.05). At the end of 14 days, the tensile strength for both materials was significantly lower in the groups modified by miconazole and itraconazole compared to the other groups (P<0.0001), which showed no significant difference between them (P>0.05). After 7 and 14 days in water, miconazole and itraconazole added into both materials result in significant lower elongation percentages compared to the other drugs and control (P<.0001), which were similar to each other (P>0.05). Ketoconazole resulted in no significant changes in PF for both liners in water over 14 days (P>0.05). Compared to the controls, Softone and Trusoft PFs were increased at 14-day water immersion only after addition of nystatin and chlorhexidine, and chlorhexidine, respectively (P<0.05). Both materials showed no significant changes in PF in up to 14 days of S50 immersion, compared to the controls (P>0.05). In all experimental conditions, Softone and Trusoft PFs were significantly lower when immersed in S50 compared to distilled water (P<0.05). It was concluded that the addition of the nystatin, chlorhexidine and ketoconazole at MICs for C. albicans biofilm resulted in no harmful effects on the ultimate tensile strength and elongation percentage of the temporary soft denture liners up to 14-day period. The addition of antifungals at MICs resulted in no detrimental effects for the porosity of both temporary soft liners in different periods of water immersion, except for chlorhexidine and nystatin in Softone and chlorhexidine in Trusoft at 14 days. No deleterious effect was observed for the porosity of both soft liners modified by the drugs at MICs over 14 days of S50 immersion.(AU)

Peel bond strength of resilient liner modified by the addition of antimicrobial agents to denture base acrylic resin

In order to prolong the clinical longevity of resilient denture relining materials and reduce plaque accumulation, incorporation of antimicrobial agents into these materials has been proposed. However, this addition may affect their properties. OBJECTIVE: This study evaluated the effect of the addition of antimicrobial agents into one soft liner (Soft Confort, Dencril) on its peel bond strength to one denture base (QC 20, Dentsply). MATERIAL AND METHODS: Acrylic specimens (n=9) were made (75x10x3 mm) and stored in distilled water at 37ºC for 48 h. The drug powder concentrations (nystatin 500,000U - G2; nystatin 1,000,000U - G3; miconazole 125 mg - G4; miconazole 250 mg - G5; ketoconazole 100 mg - G6; ketoconazole 200 mg - G7; chlorhexidine diacetate 5% - G8; and 10% chlorhexidine diacetate - G9) were blended with the soft liner powder before the addition of the soft liner liquid. A group (G1) without any drug incorporation was used as control. Specimens (n=9) (75x10x6 mm) were plasticized according to the manufacturers' instructions and stored in distilled water at 37ºC for 24 h. Relined specimens were then submitted to a 180-degree peel test at a crosshead speed of 10 mm/min. Data (MPa) were analyzed by analysis of variance (α=0.05) and the failure modes were visually classified. RESULTS: No significant difference was found among experimental groups (p=0.148). Cohesive failure located within the resilient material was predominantly observed in all tested groups. CONCLUSIONS: Peel bond strength between the denture base and the modified soft liner was not affected by the addition of antimicrobial agents.

Poly (Methyl Methacrylate) absorption and releasing of nystatin and fluconazole / Absorção e liberação de nistatina e fluconazol por polimetilmetacrilato

Objectives: The aim of this study was to verify if there are poly (methyl methacrylate) (PMMA) absorptionand releasing of nystatin (NYS) and fluconazole (FLZ) after simulated treatment of oral candidosis. Materialsand methods: Specimens (30 × 25 × 5 mm) prepared with PMMA polymerized by hot water bath or microwaveenergy were immersed into NYS (3.12 μg/mL), FLZ (2.56 μg/mL) or deionized water (control) during14 days at 35 ± 2 °C. After treatment simulation, specimens were immersed into distilled water during 3, 7, 10and 14 days. The immersion liquid was changed after each analysis. Higher performance liquid chromatographywas used in order to detect antifungal compounds. In order to determine if there was surface depositionof drugs on PMMA resin, specimens were analyzed with electronic microscopy (SEM). Results: None of theantifungal agents was released from the PMMA resins. Conclusion: Within the limitations of this study, itcould be concluded that PMMA resins had no drug absorption with posterior release.

Objetivos: O objetivo deste estudo foi verificar se o poli (metil metacrilato) (PMMA) é capaz de absorver e liberar nistatina (NYS) e fluconazol (FLZ) após simular um tratamento para candidose oral. Materiais e métodos:Espécimes (30 × 25 × 5 mm) foram preparados em resina de PMMA por banho de água quente ou energia demicro-ondas e, em seguida, imersos em solução contendo NYS (3.12 μg/mL), FLZ (2.56 μg/mL) ou água deionizada(controle) durante 14 dias a 35 ± 2 °C. Após a simulação de tratamento, os espécimes foram imersos em água destilada durante 3, 7, 10 e 14 dias. O líquido de imersão foi trocado após cada análise. Cromatografia líquida de alta performance foi utilizada para detectar a presença dos agentes antifúngicos. Para determinar se houve deposição dos agentes antifúngicos na superfície de PMMA, os espécimes foram analisados por microscopia eletrônica de varredura(MEV). Resultados: Não houve liberação de agentes antifúngicos dos espécimes. Conclusão: Considerando as limitações deste estudo, pode-se concluir que a resina de PMMA não absorve ou libera agentes antifúngicos.

Formulation and characterization of nystatin gel

The main objective of this research is to develop and characterize a series of carbopol 934 (CP) hydroxypropyl methylcellulose (HPMC) and a combination of carbopol-HPMC as a gel base for topical delivery of nystatin. The drug level was held constant at 1.72% w/w and the level of propylene glycol which is used as a co-solvent and penetration enhancer was also kept constant at 2% w/w. The total level of the polymer was held constant at 1.5% w/w as a single polymer or combination of two polymers. The polymers combination selected were: carbopol 934 to HPMC at a ratio of 0:1, 1:0, 1:2, 2:1 and 1:1. The batch size was 500 g and triethanolamine was used to adjust the pH of the gel. The rheological study showed that formulation containing combination of 2 carbopol and 1 HPMC ratio gave the highest viscosity, and exhibited an apparent pseudoplastic thixotropic behavior. The diffusion study indicated that gel formulation containing carbopol-HPMC at a ratio of 2:1 gave the highest percent drug diffusion compared to formulation containing low carbopol to HPMC ratio, carbopol alone or HPMC alone. Both in-vitro release and rheological study indicated that carbopol-HPMC had the best gel strength, physical properties and ability to diffuse the drug than carbopol or HPMC alone. The results obtained in this study demonstrated that the combination of carbopol and hydroxypropyl methylcellulose can be used as a gel vehicle for nystatin topical application.

Effects of nystatin, fluconazole and propolis on poly (methyl methacrylate) resin surface

The prevalence of candidosis in denture wearers is as well established as its treatment with antifungal agents (AAs). However, little research has been done regarding the effects of AAs on denture base surfaces. Therefore, the aim of this study was to evaluate the effects of fluconazole (FLU), nystatin (NYS) and propolis orabase gel (PRO) on poly (methyl-methacrylate) (PMMA) surfaces. Deionized water and orabase gel without any active component were used as control groups. Conventional heat-polymerized (Clássico) and microwave-polymerized (Onda Cryl) acrylic resins were used. After polymerization, the specimens were polished and had their surfaces evaluated for roughness, free energy and Knoop hardness. Subsequently, specimens were immersed in AAs and controls for 14 days at 35±2 °C and all variables were measured again. Data were analyzed statistically by 2-way ANOVA followed by Tukey's test ( α=0.05). Roughness results showed similar behavior for both PMMA resins, with PRO reaching the highest values and differing significantly from the other AAs (p<0.05). No statistically significant differences (p>0.05) were found between the two PMMA resins or between NYS and FLU as regards surface free energy. In conclusion, PRO was able to induce changes in PMMA surface properties, such as roughness, which could be related to microbial adhesion.

A alta prevalência da candidose em usuários de prótese dental removível e a sua terapêutica com agentes antifúngicos (AA) está estabelecida. Contudo, o efeito dos AA sobre a superfície da resina de poli(metil-metacrilato) (PMMA) ainda não foi estudada. Assim, objetivou-se avaliar o efeito do fluconazol (FLU), nistatina (NYS) e gel orabase de própolis (GO) sobre a superfície de PMMA. Água deionizada e GO sem princípio ativo foram utilizadas como controles. Espécimes fabricados com PMMA polimerizada em banho de água ou com energia de microondas receberam acabamento e polimento e tiveram a rugosidade de superfície (RS), energia livre de superfície (ELS) e dureza Knoop (DK) mensuradas. Os tratamentos de superfície foram obtidos pela imersão dos espécimes nos AA durante 14 dias. Os resultados obtidos foram analisados por ANOVA para dois fatores e para a comparação, entre tratamentos e resinas, o teste de Tukey (α=0,05) foi utilizado. Os resultados mostraram que ambas as resinas aumentaram RS e ELS, mas não diferiram entre si (p>0,05). Os grupos tratados com própolis mostraram valores maiores de RS e diferente dos demais AAs (p<0,05). Com relação a rugosidade e energia livre de superfície não foram encontradas diferenças entre as PMMAs e entre FLU e NYS. Concluiu-se que a própolis induziu modificações na superfície de PMMA aumentando a rugosidade, fator que poderá facilitar a adesão de microrganismos.

Synthesis, physico-chemical and biological properties of some alkali metals and quaternary alkylammonium salts of polyene antibiotics: amphotericin B, nystatin and aureofungin.

Polyene antibiotics are known for their remarkable antifungal properties. The alkali metal and quaternary alkylammonium salts of amphotericin B, nystatin and aureofungin have been prepared by ion-exchange method. The physico-chemical and biological properties of these salts have been studied with a view to evaluate their therapeutic advantages over the parent compounds. While the majority of the salts reported herein showed more water solubility; triethylammonium salts, unlike the other alkali metal salts, possessed marginally improved or similar bioactivity in comparison to their parent antibiotic having reduced toxicity.