Microparticles in the Development and Improvement of Pharmaceutical Formulations: An Analysis of In Vitro and In Vivo Studies

: Microparticulate systems such as microparticles, microspheres, microcapsules or any particle in a micrometer scale (usually of 1-1000 µm) are widely used as drug delivery systems, because they offer higher therapeutic and diagnostic performance compared to conventional drug delivery forms. These systems can be manufactured with many raw materials, especially polymers, most of which have been effective in improving the physicochemical properties and biological activities of active compounds. This review will focus on the in vivo and in vitro application in the last decade (2012 to 2022) of different active pharmaceutical ingredients microencapsulated in polymeric or lipid matrices, the main formulation factors (excipients and techniques) and mostly their biological activities, with the aim of introducing and discussing the potential applicability of microparticulate systems in the pharmaceutical field

Precipitation influence on the runoff of a small-watershed in the Federal District, Brazil

O conhecimento do escoamento superficial é importante para o dimensionamento de obras hidráulicas e para a conservação da água e do solo. O volume de água escoado superficialmente depende de fatores de natureza edafoclimática e fisiográfica da região. O objetivo deste estudo foi verificar a influência relativa do total precipitado (P), da precipitação antecedente (PA) e da intensidade de precipitação (IP) na ocorrência de eventos de escoamento superficial (Es), na microbacia do Córrego Capetinga, situada no Centro-Oeste do Brasil, região de cerrado. Foram analisados os dados de P, PA e IP obtidos durante seis anos hidrológicos, iniciando em 1º de julho de 1996 e terminando em 30 de junho 2002. Foram somente considerados valores de Es maiores ou iguais a 0,1 mm, oriundos de hidrógrafas geradas a partir dos dados de linígrafo instalado na saída da bacia. Um conjunto de 187 dados de P, PA, IP e Es foram submetidos à análise de regressão linear múltipla. Os resultados mostraram que as variáveis independentes P, PA e IP têm dupla e tríplice interação, influenciando na variável dependente Es. Por intermédio dos valores absolutos dos coeficientes de regressão, constatou-se que IP foi mais importante do que PA na estimativa da variável Es. O valor do coeficiente de escoamento superficial total médio sugere que a microbacia possui boas condições de infiltração de água no solo.The knowledge of surface runoff is important for adequate hydraulic structures designing and for soil water conservation. The total volume of water from surface runoff is dependent of local edaphic, climatic and physiographic conditions. The objective of this study was to find out the relative importance of rainfall amount (P) and intensity (IP) and antecedent precipitation (PA) on total runoff (Es) provided by the "Capetinga" stream watershed, located in Brazil mid-west savannah region. It was analyzed watershed data for a six years period beginning on July 1st, 1996, and ending on June 30th, 2002. It was considered only Es events greater or equal to 0.1 mm, measured with a stream gage located at the watershed outlet. A set of 187 P, PA, IP and Es events were submitted to a linear multiple regression analysis. The results showed that the independent variable P, PA and IP had two and three-factor interactions, influencing the dependent variable Es. Regression coefficients of absolute values evidenced that IP was more important than PA to estimate de independent variable Es. The average total runoff coefficient value suggests that the watershed has a good condition of soil water infiltration

Comparison of fast-track diagnostics respiratory pathogens multiplex real-time RT-PCR assay with in-house singleplex assays for comprehensive detection of human respiratory viruses

Fast-track Diagnostics respiratory pathogens (FTDRP) multiplex real-time RT-PCR assay was compared with in-house singleplex real-time RT-PCR assays for detection of 16 common respiratory viruses. The FTDRP assay correctly identified 26 diverse respiratory virus strains, 35 of 41 (85%) external quality assessment samples spiked with cultured virus and 232 of 263 (88%) archived respiratory specimens that tested positive for respiratory viruses by in-house assays. Of 308 prospectively tested respiratory specimens selected from children hospitalized with acute respiratory illness, 270 (87.7%) and 265 (86%) were positive by FTDRP and in-house assays for one or more viruses, respectively, with combined test results showing good concordance (K=0.812, 95% CI = 0.786-0.838). Individual FTDRP assays for adenovirus, respiratory syncytial virus and rhinovirus showed the lowest comparative sensitivities with in-house assays, with most discrepancies occurring with specimens containing low virus loads and failed to detect some rhinovirus strains, even when abundant. The FTDRP enterovirus and human bocavirus assays appeared to be more sensitive than the in-house assays with some specimens. With the exceptions noted above, most FTDRP assays performed comparably with in-house assays for most viruses while offering enhanced throughput and easy integration by laboratories using conventional real-time PCR instrumentation. Published by Elsevier B.V.High Priority Pandemic and Seasonal Influenza Scientific proposal request initiativ

Dmdmdx/Largemyd: a new mouse model of neuromuscular diseases useful for studying physiopathological mechanisms and testing therapies

Although muscular dystrophies are among the most common human genetic disorders, there are few treatment options available. Animal models have become increasingly important for testing new therapies prior to entering human clinical trials. The Dmdmdx mouse is the most widely used animal model for Duchenne muscular dystrophy (DMD), presenting the same molecular and protein defect as seen in humans with the disease. However, this mouse is not useful for clinical trials because of its very mild phenotype. The mouse model for congenital myodystrophy type 1D, Largemyd, harbors a mutation in the glycosyltransferase Large gene and displays a severe phenotype. To help elucidate the role of the proteins dystrophin and LARGE in the organization of the dystrophin-glycoprotein complex in muscle sarcolemma, we generated double-mutant mice for the dystrophin and LARGE proteins. The new Dmdmdx/Largemyd mouse model is viable and shows a severe phenotype that is associated with the lack of dystrophin in muscle. We tested the usefulness of our new mouse model for cell therapy by systemically injecting them with normal murine mesenchymal adipose stem cells (mASCs). We verified that the mASCs were hosted in the dystrophic muscle. The new mouse model has proven to be very useful for the study of several other therapies, because injected cells can be screened both through DNA and protein analysis. Study of its substantial muscle weakness will also be very informative in the evaluation of functional benefits of these therapies.FAPESP - CEPIDInstituto Nacional de Ciência e Tecnologia em Células-Tronco e Terapia Celular (INCTC) - CNPqFINEPABDIMCAPES / COFECU

Dioctadecyldimethylammonium:monoolein nanocarriers for efficient in vitro gene silencing

This study describes a novel liposomal formulation for siRNA delivery, based on the mixture of the neutral lipid monoolein (MO) and cationic lipids of the dioctadecyldimethylammonium (DODA) family. The cationic lipids dioctadecyldimethylammonium bromide (DODAB) and chloride (DODAC) were compared in order to identify which one will most efficiently induce gene silencing. MO has a fluidizing effect on DODAC and DODAB liposomes, although it was more homogeneously distributed in DODAC bilayers. All MO-based liposomal formulations were able to efficiently encapsulate siRNA. Stable lipoplexes of small size (100-160 nm) with a positive surface charge (>+45 mV) were formed. A more uniform MO incorporation in DODAC:MO may explain an increase of the fusogenic potential of these liposomes. The siRNA-lipoplexes were readily internalized by human nonsmall cell lung carcinoma (H1299) cells, in an energy dependent process. DODAB:MO nanocarriers showed a higher internalization efficiency in comparison to DODAC:MO lipoplexes, and were also more efficient in promoting gene silencing. MO had a similar gene silencing ability as the commonly used helper lipid 1,2-dioleyl-3-phosphatidylethanolamine (DOPE), but with much lower cytotoxicity. Taking in consideration all the results presented, DODAB:MO liposomes are the most promising tested formulation for systemic siRNA delivery.This work was supported by FEDER through POFC - COMPETE and by national funds from FCT through the projects PEst-C/BIA/UI4050/2011 (CBM.A), PEst-C/FIS/UI0607/2011 (CFUM), and PTDC/QUI/69795/2006, while Ana Oliveira holds scholarship SFRH/BD/68588/2010. Eloi Feitosa thanks FAPESP (2011/03566-0) and CNPq (303030/2012-7), and Renata D. Adati thanks FAPESP for scholarship (2011/07414-0). K. Raemdonck is a postdoctoral fellow of the Research Foundation - Flanders (FWO-Vlaanderen). We acknowledge NanoDelivery-I&D em Bionanotecnologia, Lda. for access to their equipment

A Formação Ambiental na Visão dos Graduandos de Licenciatura Plena em Ciências Naturais – Habilitação Química na Universidade do Estado Pará - UEPA

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Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans

Infected animals will produce reactive oxygen species (ROS) and other inflammatory molecules that help fight pathogens, but can inadvertently damage host tissue. Therefore specific responses, which protect and repair against the collateral damage caused by the immune response, are critical for successfully surviving pathogen attack. We previously demonstrated that ROS are generated during infection in the model host Caenorhabditis elegans by the dual oxidase Ce-Duox1/BLI-3. Herein, an important connection between ROS generation by Ce-Duox1/BLI-3 and upregulation of a protective transcriptional response by SKN-1 is established in the context of infection. SKN-1 is an ortholog of the mammalian Nrf transcription factors and has previously been documented to promote survival, following oxidative stress, by upregulating genes involved in the detoxification of ROS and other reactive compounds. Using qRT-PCR, transcriptional reporter fusions, and a translational fusion, SKN-1 is shown to become highly active in the C. elegans intestine upon exposure to the human bacterial pathogens, Enterococcus faecalis and Pseudomonas aeruginosa. Activation is dependent on the overall pathogenicity of the bacterium, demonstrated by a weakened response observed in attenuated mutants of these pathogens. Previous work demonstrated a role for p38 MAPK signaling both in pathogen resistance and in activating SKN-1 upon exposure to chemically induced oxidative stress. We show that NSY-1, SEK-1 and PMK-1 are also required for SKN-1 activity during infection. Evidence is also presented that the ROS produced by Ce-Duox1/BLI-3 is the source of SKN-1 activation via p38 MAPK signaling during infection. Finally, for the first time, SKN-1 activity is shown to be protective during infection; loss of skn-1 decreases resistance, whereas increasing SKN-1 activity augments resistance to pathogen. Overall, a model is presented in which ROS generation by Ce-Duox1/BLI-3 activates a protective SKN-1 response via p38 MAPK signaling

The impact of SARS-CoV-2 in dementia across Latin America : A call for an urgent regional plan and coordinated response

The SARS-CoV-2 global pandemic will disproportionately impact countries with weak economies and vulnerable populations including people with dementia. Latin American and Caribbean countries (LACs) are burdened with unstable economic development, fragile health systems, massive economic disparities, and a high prevalence of dementia. Here, we underscore the selective impact of SARS-CoV-2 on dementia among LACs, the specific strain on health systems devoted to dementia, and the subsequent effect of increasing inequalities among those with dementia in the region. Implementation of best practices for mitigation and containment faces particularly steep challenges in LACs. Based upon our consideration of these issues, we urgently call for a coordinated action plan, including the development of inexpensive mass testing and multilevel regional coordination for dementia care and related actions. Brain health diplomacy should lead to a shared and escalated response across the region, coordinating leadership, and triangulation between governments and international multilateral networks