Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities.

This review aims to provide an overview of studies that address the use, in therapeutic applications, of solid dispersions (SDs) with biological activities in vitro and/or in vivo mainly made up of polymeric matrices, as well as to evaluate the bioactive activity of their constituents. This bibliographic survey shows that the development of solid dispersions provides benefits in the physicochemical properties of bioactive compounds, which lead to an increase in their biological potential. However, despite the reports found on solid dispersions, there is still a need for biological assay-based studies, mainly in vivo, to assist in the investigation and to devise new applications. Therefore, studies based on such an approach are of great importance to enhance and extend the use of solid dispersions in the most diverse therapeutic applications.

Evaluation of the serum biochemistry and histopathology of kidney and bladder of dogs with Leishmania sp. in their urine / Avaliação da bioquímica sérica e histopatologia de rim e bexiga de cães com Leishmania sp. na urina

The visceral establishment of Leishmania infantum in dogs may result in kidney and bladder tissue injury, with L. infantum ending up in urine. This study therefore aimed at investigating the presence of Leishmania sp. in urinary sediments, and correlating the results with those from renal and bladder serum biochemistry and histopathology. Thirty dogs with negative Nested-Polymerase Chain Reaction (PCR) for E. canis were used in the experiment, and were divided into three groups: control group (10 dogs), neither leishmaniasis nor clinical changes; group I (15 dogs), leishmaniasis but no Leishmania sp. in urine; and group II (5 dogs), leishmaniasis, as well as Leishmania sp. in urine. All animals were submitted to clinical, serological, and parasitological diagnosis for leishmaniasis, biochemical exams, and kidney and bladder histopathology. The parasite was also detected in the bladder imprint of one group II dog. Group II dogs presented with very low albumin concentrations, low albumin/globulin ratios, and kidney and bladder lesions. In the kidneys, hydropic degeneration, thickened Bowman's capsule, and thickening of the tubular capsule were detected in all dogs with positive urinary sediment. However, no significant difference in these renal changes was observed between groups. The intensity and distribution of bladder inflammatory infiltrates were significantly (p-value < 0.05, Kruskal-Wallis' and Dunn's tests) higher in group II dogs, compared with those of the other groups. The presence of Leishmania sp.in the urine of infected dogs appeared to be related to low serum albumin concentrations and more severe bladder lesions

O estabelecimento visceral de Leishmania infantum em cães pode resultar em lesões nos tecidos dos rins e da bexiga, favorecendo a chegando do parasito até a urina. Portanto, este estudo teve como objetivo investigar a presença de Leishmania sp. em sedimentos urinários e correlacionar os resultados com os achados de quantificações bioquímicas séricas e histopatologia de rim e bexiga. Trinta cães com Nested-Reação em Cadeia da Polimerase (PCR) negativa para E. canis foram utilizados no experimento e foram divididos em três grupos: grupo controle (10 cães), negativos para leishmaniose e sem alterações clínicas; grupo I (15 cães), com leishmaniose, mas sem Leishmania sp. na urina; e grupo II (5 cães), com leishmaniose e com Leishmaniasp. na urina. Todos os animais foram submetidos a diagnóstico clínico, sorológico e parasitológico para leishmaniose, exames bioquímicos e histopatologia de rim e bexiga. O parasito foi detectado no imprimt de bexiga de um cão do grupo II. Os cães do grupo II apresentaram concentrações muito baixas de albumina, baixa relação albumina/globulina e lesões nos rins e na bexiga. Nos rins, foram detectadas degeneração hidrópica, espessamento da cápsula de Bowman e espessamento da cápsula tubular, em todos os cães com sedimento urinário positivo. No entanto, nenhuma diferença significativa nessas alterações renais foi observada entre os grupos. A intensidade e a distribuição dos infiltrados inflamatórios da bexiga foram significativamente (p-valor < 0,05, testes de Kruskal-Wallis e Dunn) maiores nos cães do grupo II, em comparação com a dos outros grupos. A presença de Leishmania sp. na urina de cães infectados parece estar relacionada a baixa concentração sérica de albumina e a lesões mais graves na bexiga.

Gallic and ellagic acids: two natural immunomodulator compounds solve infection of macrophages by Leishmania major.

Leishmaniasis is a complex of parasitic protozoan diseases caused by more than 20 different species of parasites from Leishmania genus. Conventional treatments are high costly, and promote a sort of side effects. Besides, protozoan resistance to treatments has been reported. Natural products have been investigated as a source of new therapeutic alternatives, not only acting directly against the parasite but also being able to synergistically act on the host immune system in order to control parasitemia. Gallic acid (GA) and ellagic acid (EA) are plant-derived phenolic compounds which are able to induce antiinflammatory, gastroprotective, and anticarcinogenic activities. Therefore, the antileishmania, cytotoxic, and immunomodulatory activities of GA and EA were evaluated in this study. Both GA and EA were able to inhibit the growth of Leishmania major promastigotes (effective concentration (EC50) values 16.4 and 9.8 µg/mL, respectively). The cytotoxicity against BALB/c murine macrophages for GA and EA was also assessed (CC50 values 126.6 and 23.8 µg/mL, respectively). Interestingly, GA and EA also significantly reduced the infection and infectivity of macrophages infected by L. major (EC50 values 5.0 and 0.9 µg/mL, respectively), with selectivity index higher than 20. Furthermore, both GA and EA induced high immunomodulatory activity evidenced by the increase of phagocytic capability, lysosomal volume, nitrite release, and intracellular calcium [Ca2+i] in macrophages. Further investigations are reinforced in order to evaluate the therapeutic effects of GA and EA in in vivo experimental infection model of leishmaniasis.