Self-assembled guanosine-hydrogels for drug-delivery application: Structural and mechanical characterization, methylene blue loading and controlled release.

It is known that guanosine derivatives (G) self-assemble in water forming long, flexible, and interacting aggregates (the so-called G-quadruplexes): by modulating the quadruplex charges, e.g. simply using a mixture of guanosine 5'-monophosphate (GMP) and guanosine (Gua), multi-responsive, self-healing hydrogels can be obtained. In this paper, the potential application of G-hydrogels as drug delivery systems has been assessed. Hydrogels were prepared at different Gua:GMP molar ratios. The photosensitizer Methylene Blue and the pro-apoptotic protein cytochrome C were used as cargo molecules. Small angle x-ray scattering and atomic force microscopy experiments confirmed the presence of G-quadruplexes disposed in swollen matrices with different mesh-sizes. Rheology measurements showed that the Gua:GMP molar ratio leads to specific drug release mechanisms, as the gel strength is finely tuned by electrostatic repulsion and van der Waals attraction between G-quadruplexes. Noteworthy, the gel cohesion and the drug release were pH responsive. Swelling, self-healing and cell viability features were also investigated: the results qualify the Gua:GMP hydrogel as an excellent biomaterial that can entrap and deliver key biomolecules in a sustained and responsive release manner.

Randomized controlled clinical trial of ketoanalogues supplementation in dogs with chronic kidney disease / Estudo clínico randomizado controlado da suplementação de cetoanálogos em cães com doença renal crônica

The objective was to verify the effectiveness of ketoanalogues in dogs with Chronic Kidney Disease (CKD) stage 3. Controlled randomized clinical trial was performed with twenty dogs with CKD stage 3. Animals were subjected to: Group 1 (control): conventional therapy (CT) for CKD; Group 2: CT and 60mg/kg, OA, q48h of keto-supplementa; Group 3, CT and 60mg/kg, OA, q24h of keto-supplementa; and Group 4, CT and 120mg/kg, OA, q12h of keto-supplementa. All dogs received canine renal diet. Animals were evaluated at the beginning of therapy and after 15 and 30 days. Complete blood count (CBC), serum urea, creatinine, phosphorus, calcium, potassium and sodium and urine protein/creatinine (UPC) ratio were analyzed. The use of ketoanalogues in dogs with CKD stage 3 during the period of 30 days showed no efficacy, in any of the studies dosages, to improve signs and symptoms of the disease, improve the values of CBC, reduce serum urea and creatinine, normalize electrolytes or reduce UPC. It is concluded that the use of ketoanalogues does not impact the clinical outcomes in dogs with CKD stage 3.(AU)

O objetivo foi de verificar a eficácia da suplementação com cetoanálogos em cães com Doença Renal Crônica (DRC) grau 3. Um ensaio clínico controlado e randomizado foi realizado com 20 cães com DRC grau 3. Os animais foram divididos em 4 grupos: grupo 1 (controle): terapia convencional (TC) para DRC; grupo 2: TC e 60mg/kg, VO, q48h de cetoanálogoa; grupo 3: TC e 60mg/kg, VO, q24h de cetoanálogoa; e grupo 4, TC e 120mg/kg, VO, q12h de cetoanálogoa. Todos os cães receberam ração renal para cães. Os animais foram avaliados no início da terapia e após 15 e 30 dias. Hemograma completo, ureia, creatinina, fósforo, cálcio, potássio e sódio séricos e a razão proteína creatinina (RPC) urinária foram analisados. Foi verificado que o uso dos cetoanálogos em cães com DRC grau 3 durante 30 dias não mostrou eficácia, em nenhuma das dosagens utilizadas, em melhorar os sinais clínicos e sintomatologia da doença, os valores do hemograma e ureia e creatinina séricos, normalizar eletrólitos e reduzir RPC. Concluiu-se que o uso de cetoanálogos não impacta na melhora de sintomatologia clínica em cães com CKD grau 3. Como esse parece ser o primeiro ensaio clínico sobre cetoanálogos em cães com CKD, mais estudos podem ser necessários com maior acompanhamento e maiores grupos.(AU)