Development of microemulsion of tamsulosin and dutasteride for benign prostatic hyperplasia therapy.

Benign prostatic hyperplasia (BPH) is a condition characterized by a benign enlargement of the prostate that interferes with the normal flow of urine. This disease is treated with the oral administration of combination therapy comprising α-blockers (tamsulosin) and 5α-reductase inhibitors (dutasteride). However, these compounds have low bioavailability. Thus, transdermal microemulsions aimed at promoting permeation and efficient targeted drug delivery through the skin are used. The objectives of this study were to obtain microemulsions of the combined doses of dutasteride and tamsulosin and evaluate their anti-hyperplastic activity in vivo. A phase diagram (4:1) was obtained for the choice of microemulsions. The microemulsions were characterized in terms of the droplet size, rheology, pH, conductivity, refractive index, in vitro release profile, and antihyperplastic effect in vivo. A method for the simultaneous quantification of drugs was developed using UV-vis spectroscopy. The microemulsions had an average size less than 116 nm, an acidic pH and low viscosity. The conductivity ranged from 6.18 to 185.2 µS/cm. The in vitro release profile was sustained for 6 h. Microemulsions promoted the reduction in the size of testosterone-dependent organs (prostate and seminal vesicles). Transdermal formulations for the treatment of BPH were obtained as a therapeutic alternative to conventional treatments.

Efeito do extrato etanólico de Simarouba versicolor em padrões reprodutivos de camundongos e no desenvolvimento embriofetal / Effect of ethanol extract of Simarouba versicolor in reproductive patterns of mice and embryo development

Simarouba versicolor has several proven biological activities, however little is known regarding effectson reproduction, so this study evaluated the effect of the ethanol extract of S. versicolor (EOH-Sv) embryofoetaldevelopment. It used to females pregnant randomly assigned into three groups receiving the extract of S.versicolor in doses of 5mg, 10mg and 20mg and a control group (-) received DMSO (3%) from the 8th to 12thday of gestation. The half of the fetuses was set at Bodian for visceral analysis, while the other half fixed informalin (5%) and subjected to alizarin red technique. The EOH-Sv at doses of 20 and 10mg caused abortionand death of the females and the dose of 5mg/kg was able to reduce the number of live fetuses compared tocontrols, there was an increase in the loss rate after implantation (46,03%) even with 90% of implantation. ThusEOH-Sv demonstrated maternal and fetal gestational toxicity.(AU)

Efeito do extrato etanólico de Simarouba versicolor em padrões reprodutivos de camundongos e no desenvolvimento embriofetal / Effect of ethanol extract of Simarouba versicolor in reproductive patterns of mice and embryo development

Simarouba versicolor has several proven biological activities, however little is known regarding effectson reproduction, so this study evaluated the effect of the ethanol extract of S. versicolor (EOH-Sv) embryofoetaldevelopment. It used to females pregnant randomly assigned into three groups receiving the extract of S.versicolor in doses of 5mg, 10mg and 20mg and a control group (-) received DMSO (3%) from the 8th to 12thday of gestation. The half of the fetuses was set at Bodian for visceral analysis, while the other half fixed informalin (5%) and subjected to alizarin red technique. The EOH-Sv at doses of 20 and 10mg caused abortionand death of the females and the dose of 5mg/kg was able to reduce the number of live fetuses compared tocontrols, there was an increase in the loss rate after implantation (46,03%) even with 90% of implantation. ThusEOH-Sv demonstrated maternal and fetal gestational toxicity.

Atividade antiandrogênica no tratamento da hiperplasia prostática benigna com nanocarreadores transdérmicos de dose combinada (tansulosina e dutasterida) / Antiandrogenic activity in Benign Prostatic Hyperplasia treatment with combined nanocarriers transdermal dose (tamsulosin and dutasteride)

Benign prostatic hyperplasia (BPH) is one of the most common diseases of the urogenital tract. Thisstudy aimed to obtain one transdermal microemulsion of dutasteride and tamsulosin, drugs used in the treatmentof BPH, characterize them and study your in vitro release, evaluating through in vivo studies the antiandrogenicactivity of transdermal microemulsion. The preparation of the formulation involved obtaining the microemulsionwith Dutasteride and Tamsulosin in the equivalent percentage of 0.2% for each drug. To carry out theantiandrogenic activity, were used 32 rats (Wistar) in four groups experimental. The characterization performedall formulations showed good results, in which the evaluation of anti-hyperplastic the microemulsiondemonstrated one reducing the organs testosterone-dependent (prostate and seminal vesicles) corroborated forthe study in question enabling then obtaining promising transdermal formulations for BPH treatment, presentingthus a therapeutic alternative to conventional treatments.(AU)

Estudo histopatológico dos órgãos reprodutivos de ratos tratados com extrato etanólico de Simarouba versicolor em ensaio de toxicidade sub-crônica / Histopathological study of the reproductive organs of rats treated with ethanol extract of Simarouba versicolor in test sub-chronic toxicity

The aim of this study was to evaluate the reproductive organs on the effect of Simarouba versicolorethanol extract (EEOH-Sv) at a dose of 10mg / kg administered for 60 days / VO. The testes, epididymis,prostate and seminal vesicles were sectioned and placed in vials Boan solution for 24 hours and then preservedin alcohol at 70%. Histopathology of organs were dehydrated in xylol, impregnated and embedded in paraffin.Subsequently cut in the microtome at a thickness of 3 m and subjected to hematoxylin-eosin. The results of thehistopathology of the testis was observed that the EEOH-Sv caused concretions in 100% of animals evaluatedand 20% of the animals showed sharp associated with degeneration of the seminiferous tubules. In theepididymis was observed in 40% epithelial thickening, and there was 100% of benign prostatic hypertrophyassociated in 20% of animals inflammatory infiltrate. Thus, it is concluded that-Sv EEOH was toxic to thisorgans except the seminal vesicle.(AU)

Estudo histopatológico dos órgãos reprodutivos de ratos tratados com extrato etanólico de Simarouba versicolor em ensaio de toxicidade sub-crônica / Histopathological study of the reproductive organs of rats treated with ethanol extract of Simarouba versicolor in test sub-chronic toxicity

The aim of this study was to evaluate the reproductive organs on the effect of Simarouba versicolorethanol extract (EEOH-Sv) at a dose of 10mg / kg administered for 60 days / VO. The testes, epididymis,prostate and seminal vesicles were sectioned and placed in vials Boan solution for 24 hours and then preservedin alcohol at 70%. Histopathology of organs were dehydrated in xylol, impregnated and embedded in paraffin.Subsequently cut in the microtome at a thickness of 3 m and subjected to hematoxylin-eosin. The results of thehistopathology of the testis was observed that the EEOH-Sv caused concretions in 100% of animals evaluatedand 20% of the animals showed sharp associated with degeneration of the seminiferous tubules. In theepididymis was observed in 40% epithelial thickening, and there was 100% of benign prostatic hypertrophyassociated in 20% of animals inflammatory infiltrate. Thus, it is concluded that-Sv EEOH was toxic to thisorgans except the seminal vesicle.

Atividade antiandrogênica no tratamento da hiperplasia prostática benigna com nanocarreadores transdérmicos de dose combinada (tansulosina e dutasterida) / Antiandrogenic activity in Benign Prostatic Hyperplasia treatment with combined nanocarriers transdermal dose (tamsulosin and dutasteride)

Benign prostatic hyperplasia (BPH) is one of the most common diseases of the urogenital tract. Thisstudy aimed to obtain one transdermal microemulsion of dutasteride and tamsulosin, drugs used in the treatmentof BPH, characterize them and study your in vitro release, evaluating through in vivo studies the antiandrogenicactivity of transdermal microemulsion. The preparation of the formulation involved obtaining the microemulsionwith Dutasteride and Tamsulosin in the equivalent percentage of 0.2% for each drug. To carry out theantiandrogenic activity, were used 32 rats (Wistar) in four groups experimental. The characterization performedall formulations showed good results, in which the evaluation of anti-hyperplastic the microemulsiondemonstrated one reducing the organs testosterone-dependent (prostate and seminal vesicles) corroborated forthe study in question enabling then obtaining promising transdermal formulations for BPH treatment, presentingthus a therapeutic alternative to conventional treatments.