Desenvolvimento de nanoconjugados de sílica mesoporosa com nutracêuticos

Resveratrol (RSV) is a nutraceutical naturally present in various foods such as red wine, grape skins, peanuts, among many others. This compound has beneficial properties for human health such as antioxidant, anti-inflammatory and anticancer activities, among others. However, due to is physicochemical characteristics, mainly its low solubility in water that results in low bioavailability, the applicability of this compound is limited. In order to overcome these limitations, nanocarriers based approaches have emerged in the last years. The present work shows the results of the synthesis and characterization of mesoporous silica nanoparticles (MSNs) and evaluates their capacity to encapsulate and in vitro release RSV. With this purpose several synthesis conditions were investigated and two RSV loading methods were tested, by immersion and evaporation. The latter proved to be more effective allowing higher loads. The in vitro release studies suggest an increase in water solubility of the encapsulated RSV, when compared to the free one, and a faster release in acidic medium.O resveratrol (RSV) é um nutracêutico naturalmente presente em diversos alimentos como o vinho tinto, casca de uva, amendoim entre outros. Possui propriedades benéficas para a saúde humana como atividade antioxidante, anti-inflamatória e anticancerígena, entre outras. Porém, devido às características físico-químicas que apresenta, principalmente baixa solubilidade em água e biodisponibilidade, a sua aplicabilidade é limitada. Nos últimos anos, para contornar estas limitações têm sido desenvolvidas abordagens baseadas em nanotransportadores. Este trabalho apresenta os resultados da síntese e caracterização de nanopartículas de sílica mesoporosas (MSNs) e avalia a sua capacidade de encapsular e libertar, em condições in vitro, o RSV. Com este propósito foram estudadas várias condições de síntese e dois métodos de carregamento foram testados, por imersão e evaporação. O último mostrou ser mais eficaz permitindo carregamentos mais elevados. Os estudos de libertação in vitro sugerem um aumento da solubilidade em água do RSV encapsulado, relativamente à sua forma livre, bem como uma libertação mais rápida em meio ácido.Mestrado em Biotecnologi

Silica-Based Nanomaterials for Diabetes Mellitus Treatment

Diabetes mellitus, a chronic metabolic disease with an alarming global prevalence, is associated with several serious health threats, including cardiovascular diseases. Current diabetes treatments have several limitations and disadvantages, creating the need for new effective formulations to combat this disease and its associated complications. This motivated the development of therapeutic strategies to overcome some of these limitations, such as low therapeutic drug bioavailability or poor compliance of patients with current therapeutic methodologies. Taking advantage of silica nanoparticle characteristics such as tuneable particle and pore size, surface chemistry and biocompatibility, silica-based nanocarriers have been developed with the potential to treat diabetes and regulate blood glucose concentration. This review discusses the main topics in the field, such as oral administration of insulin, glucose-responsive devices and innovative administration routes

Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy

Melanoma incidence, a type of skin cancer, has been increasing worldwide. There is a strong need to develop new therapeutic strategies to improve melanoma treatment. Morin is a bioflavonoid with the potential for use in the treatment of cancer, including melanoma. However, therapeutic applications of morin are restrained owing to its low aqueous solubility and limited bioavailability. This work investigates morin hydrate (MH) encapsulation in mesoporous silica nanoparticles (MSNs) to enhance morin bioavailability and consequently increase the antitumor effects in melanoma cells. Spheroidal MSNs with a mean size of 56.3 ± 6.5 nm and a specific surface area of 816 m2/g were synthesized. MH was successfully loaded (MH-MSN) using the evaporation method, with a loading capacity of 28.3% and loading efficiency of 99.1%. In vitro release studies showed that morin release from MH-MSNs was enhanced at pH 5.2, indicating increased flavonoid solubility. The in vitro cytotoxicity of MH and MH-MSNs on human A375, MNT-1 and SK-MEL-28 melanoma cell lines was investigated. Exposure to MSNs did not affect the cell viability of any of the cell lines tested, suggesting that the nanoparticles are biocompatible. The effect of MH and MH-MSNs on reducing cell viability was time- and concentration-dependent in all melanoma cell lines. The A375 and SK-MEL-28 cell lines were slightly more sensitive than MNT-1 cells in both the MH and MH-MSN treatments. Our findings suggest that MH-MSNs are a promising delivery system for the treatment of melanoma

Isolated diastolic potentials as predictors of success in ablation of right ventricular outflow tract idiopathic premature ventricular contractions.

BACKGROUND AND AIMS:Discrete potentials, low voltage and fragmented electrograms, have been previously reported at ablation site, in patients with premature ventricular contractions (PVCs) originating in the right ventricular outflow tract (RVOT). The aim of this study was to review the electrograms at ablation site and assess the presence of diastolic potentials and their association with success. METHODS:We retrospectively reviewed the electrograms obtained at the radiofrequency (RF) delivery sites of 48 patients subjected to ablation of RVOT frequent PVCs. We assessed the duration and amplitude of local electrogram, local activation time, and presence of diastolic potentials and fragmented electrograms. RESULTS:We reviewed 134 electrograms, median 2 (1-4) per patient. Success was achieved in 40 patients (83%). At successful sites the local activation time was earlier- 54 (-35 to -77) ms vs -26 (-12 to -35) ms, p<0.0001; the local electrogram had lower amplitude 1 (0.45-1.15) vs 1.5 (0.5-2.1) mV, p = 0.006, and longer duration 106 (80-154) vs 74 (60-90) ms, p<0.0001. Diastolic potentials and fragmented electrograms were more frequently present, respectively 76% vs 9%, p <0.0001 and 54% vs 11%, p<0.0001. In univariable analysis these variables were all associated with success. In multivariable analysis only the presence of diastolic potentials [OR 15.5 (95% CI: 3.92-61.2; p<0.0001)], and the value of local activation time [OR 1.11 (95% CI: 1.049-1.172 p<0.0001)], were significantly associated with success. CONCLUSION:In this group of patients the presence of diastolic potentials at the ablation site was associated with success