Poloxamer-enhanced solubility of griseofulvin and its related antifungal activity against Trichophyton spp

Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.

In Vitro additive effect on griseofulvin and terbinafine combinations against multidrug-resistant dermatophytes

ABSTRACT Griseofulvin (GF) and terbinafine (TF) are commonly used drugs to treat dermatophytosis, a fungal infection of the skin. Today there is an increase in drug resistance to these antifungals which highlight the need for alternative synergistic therapies. Minimum Inhibitory Concentration (MIC) of GF and TF were determined against fungi clinical isolates from local hospitals with values ranging 0.03-2.0 µg mL-1 and 0.24-4.0 µg mL-1, respectively. A checkboard test was used to determine the combination of GF:TF which could induce an additive effect against the fungi isolates Multidrug-resistant isolates showed susceptibility after treatment with 16:2 µg mL-1 GF:TF. An MTT assay further verified that GF and TF combinations have greater additive effect against pathological and multidrug-resistant isolates than antifungals alone. Herein we disclose GF:TF combinations that could constitute as a possible new anti-dermatophyte therapy.

Evaluation of foam properties of saponin from Ilex paraguariensis A. St. Hil. (Aquifoliaceae) fruits

Saponins are natural compounds able to form abundant foam, a desirable quality required in some chemical, foods, cosmetic and pharmaceutical processes. Ilex paraguariensis A. St. Hil. (Aquifoliaceae) known as mate, is a South American widely cultivated specie due to the preparation of a tea-like beverage from its leaves. Moreover, its green fruits are a rich source of non-toxic and very low haemolytic saponins. In this study, mate saponin fraction (MSF) was evaluated as a foam former, focusing on its foamability, foam lifetime, and film drainage in the presence of different electrolytes (ionic strength I = 0.024 M). Sodium dodecyl sulphate (SDS) and polysorbate 80 (Poly-80) were used as reference surfactants. The critical micelle concentration (CMC), the minimum attainable surface tension (γCMC), surface excess concentration (Γ) and cross-section molecular surface (A) values of MSF were comparable to those of Poly-80. The foamability of MSF and both reference surfactants was equivalent. The addition of MgCl2 resulted in a negative effect on MSF foamability. The salts NaCl, KBr, and KNO3 exhibited a negative influence on MSF foam lifetime. Similar behavior was observed for MSF film drainage (order of activity: Na2HPO4 > MgCl2 ≈ NaCl ≈ KNO3 > KBr), where a primary fast film drainage rate was followed by film thinning stabilization after around 5 min. The behavior described above seems to be uncorrelated to the solutions' zeta potential.

As saponinas são compostos naturais capazes de formar espuma abundante, qualidade desejável exigida em alguns processos químicos, alimentícios, cosméticos e farmacêuticos. Ilex paraguariensis A. St. Hil. (Aquifoliaceae), mais conhecida como mate, é uma espécie largamente cultivada devido ao consumo do chimarrão. Além disso, seus frutos verdes representam uma fonte rica de saponinas pouco tóxicas e pouco hemolíticas. Nesse trabalho avaliou-se a fração de saponinas de mate (MSF) como formadora de espuma, com ênfase na espumabilidade, permanência da espuma e drenagem do filme na presença de diferentes eletrólitos (I = 0,024 M). Dodecil sulfato de sódio (SDS) e polissorbato 80 (Poly-80) foram utilizados como tensoativos-referência. Os valores de concentração micelar crítica (CMC), tensão superficial na CMC (γCMC), concentração de excesso de superfície (Γ) e área do grupamento polar na interface (A) referente à MSF foram comparáveis ao Poly-80. A espumabilidade da MSF e de ambos os tensoativos-referência foram equivalentes. A adição de MgCl2 resultou em um efeito negativo sobre a espumabilidade de MSF. Os sais NaCl, KBr e KNO3 tiveram influência negativa sobre a estabilidade da espuma. Em relação à drenagem do filme de MSF, após 60 min. seguiu-se a ordem Na2HPO4 > MgCl2 ≈ NaCl ≈ KNO3 > KBr, caracterizando uma drenagem inicial acelerada seguida pelo equilíbrio hidrodinâmico do filme após 5 min. O comportamento observado parece não estar relacionado com o potencial zeta das soluções.

Aminoácidos näo protéicos de Ateleia glazioviana Baillon / Non-proteinogenic aminoacids from Ateleia glazioviana Baillon

Ateleia glazioviana Baillon, Leguminosae-Papilionoideae, árvore de ocorrência na regiäo de Palmeira das Missöes (RS), possui atividade tóxica para o gado, ictiotóxica e repelente de insetos, referida por populares do interior do estado. Do extrato de sementes e pericarpo alado, foram isolados três aminoácidos näo protéicos, dois dos quais identificados como ácido 1-aminociclobutano -1,3-dicarboxílico e Ð-acetilomitina

Rotina em folhas de Ateleia glazioviana Baill (Leguminosae - Papilionoideae) / Rutin in leaves of Ateleia glazioviana Baill (Leguminosae - Papilionoideae)

O teor de rutina foi avaliado em extratos hidroalcoólicos de folha de Ateleia glazioviana Baill. Foram examinadas amostras coletadas em janeiro, maio, outubro e dezembro, constatando-se maior teor na amostra de outubro (primavera). Com o produto bruto e purificado obtido dessa amostra foram realizados ensaios de pureza e doseamento da rutina conforme F. Bras. III.

The hydroalcoholic extracts from dried leaves of Ateleia glazioviana Baill (Leguminosae - Papilionoideae) yeld rutin as one of the main compounds. Samples collected in January, May, October and December were evaluated. Analysis of the obtained rutin was performed according to F. Bras. III.

Isoflavonas de Ateleia glazioviana Baillon (Leguminosae) / Isoflavones of Ateleia glazioviana Baillon (Leguminosae)

De caule e folhas de Ateleia glazioviana Baillon foram isoladas afrormosina e 5-metoxiafrormosina