Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line.

O ácido ursólico é um candidato promissor para o tratamento da doença de Chagas, contudo este fármaco possui baixa solubilidade aquosa e limitada absorção intestinal, ambos os fatores limitantes da biodisponibilidade. Entre as estratégias para potencializar a solubilidade e a dissolução de fármacos lipofílicos, as dispersões sólidas estão crescendo em popularidade. Neste estudo, empregamos mistura dos tensoativos, poloxamer 407 e caprato de sódio, para produzir dispersão sólida contendo ácido ursólico, com o objetivo de aumentar tanto a dissolução do fármaco quanto a atividade tripanocida in vivo. Comparada à mistura física, a dispersão sólida apresentou maior densidade e menor tamanho de partícula. Os resultados da análise de espectroscopia no infravermelho com transformada de Fourier mostraram interações intermoleculares do tipo ligações de hidrogênio entre o fármaco e o poloxamer 407. Os experimentos de difratometria de raio-X revelaram a conversão do fármaco de sua forma cristalina para a forma amorfa, mais solúvel. Consequentemente, a solubilidade do ácido ursólico em dispersão sólida foi aumentada e o fármaco dissolveu-se de maneira mais rápida e completa. Em conjunto com as propriedades promotoras de absorção oral do caprato de sódio, estes resultados explicaram o aumento da atividade tripanocida in vivo do ácido ursólico em dispersão sólida, que também se provou segura após avaliação de citotoxicidade empregando a linhagem celular LLC-MK2.

Influence of concentration, time and method of application of citric acid and sodium citrate in root conditioning

OBJECTIVES: The aim of this study was to establish the parameters of concentration, time and mode of application of citric acid and sodium citrate in relation to root conditioning. MATERIAL AND METHODS: A total of 495 samples were obtained and equally distributed among 11 groups (5 for testing different concentrations of citric acid, 5 for testing different concentrations of sodium citrate and 1 control group). After laboratorial processing, the samples were analyzed under scanning electron microscopy. A previously calibrated and blind examiner evaluated micrographs of the samples. Non-parametric statistical analysis was performed to analyze the data obtained. RESULTS: Brushing 25% citric acid for 3 min, promoted greater exposure of collagen fibers in comparison with the brushing of 1% citric acid for 1 minute and its topical application at 1% for 3 min. Sodium citrate exposed collagen fibers in a few number of samples. CONCLUSION: Despite the lack of statistical significance, better results for collagen exposure were obtained with brushing application of 25% citric acid for 3 min than with other application parameter. Sodium citrate produced a few number of samples with collagen exposure, so it is not indicated for root conditioning.

Evaluation of semen quality in a local Libyan population.

Semen analyses was carried out in a population of 1250 randomly selected Libyan males. Two semen samples collected from each volunteer were subjected to the routine analyses following the World Health Organization recommendations. The Libyan population had a higher percentage of men with sperm density in the range of 40-60 millions/ml. The percentage of men with sperm counts above 100 millions/ml is comparatively lower than that is reported by MacLeod and Gold (9). The seminal plasma transferrin levels showed a positive correlation with sperm density and alpha-glucosidase activity with sperm motility.

Bioquímica do líquido espermático: relaçäo entre as dosagens de frutose e ácido cítrico e a contagem de espermatozóides / Seminal fluid biochemistry: fructose and citric acid dosages and their correlation with sperm count

Foram estudadas 300 amostras de líquido espermático de pacientes normospérmicos que näo apresentavam evidências de patologias das glândulas acessórias do trato reprodutor masculino ou de deficiência hormonal androgênica. Em todas as amostras realizou-se as dosagens bioquímicas de frutose e ácido cétrico correlacionando-as com a srespectivas contagens de espermatozóides. A análise revelou näo haver diferenca significativa entre os grupos estudados quanto às concentraçöes de frutose e ácido cítrico (p > 0,05) em relaçäo ao número de espermatozóides presentes nas amostras

Dosagem do ácido cítrico no esperma: método simplificado / Dosage of citric acid in sperma: a simplified method

Autores utilizam a técnica de Chambon, para a dosagem de ácido cítrico no esperma suprimindo a fase de desproteinizaçäo do líquido seminal. Obtiveram um método reprodutível e compatível com os quadros clínicos estudados

Seminal fructose, citric acid and phosphatase levels and their relation to the sperm count in man.

Seminal fructose, citric acid and phosphatase levels were estimated in 60 normal adults and compared with 60 oligospermic and 24 azoospermic Indian subjects. In normal group, the seminal plasma fructose level and acid phosphatase activity showed a fall as the sperm count increased. As compared to normals, significantly higher mean values for fructose and acid phosphatase activity were observed in oligospermic and azoospermic groups. Seminal alkaline phosphatase activity did not show any relationship with sperm count. Similarity in changes observed in seminal fructose and acid phosphatase levels with respect to seminal citric acid content and sperm concentration suggests that both these parameters are probably regulated by similar physiological mechanism.