Validação de metodologia analítica por cromatografia líquida de alta eficiência para quantificação de bupivacaína (S75-R25) em nanoesferas de poli(lactídeo-co-glicolídeo)

Bupivacaine (S75-R25, NovaBupi®) is an amide type local anesthetic widely used. The present work consists of the development and validation of analytical methodology for evaluation of NovaBupi® content in the poly-lactide-co-glycolide nanospheres (PLGA-NS) by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/phosphate buffer 85:15 v/v as mobile phase and detection at 220 nm. The results obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 10-220.0 g/mL of NovaBupi®. The method was applied to determine the encapsulation efficiency and evaluate the release profile of NovaBupi®, showing good results

Validation of analytical methodology by HPLC for quantification of bupivacaine (S75-R25) in poli-lactide-co-glicolide nanospheres

Bupivacaine (S75-R25, NovaBupi®) is an amide type local anesthetic widely used. The present work consists of the development and validation of analytical methodology for evaluation of NovaBupi® content in the poly-lactide-co-glycolide nanospheres (PLGA-NS) by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/phosphate buffer 85:15 v/v as mobile phase and detection at 220 nm. The results obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 10-220.0 g/mL of NovaBupi®. The method was applied to determine the encapsulation efficiency and evaluate the release profile of NovaBupi®, showing good results.21522155Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Magnetic nanostructures for emerging biomedical applications

Magnetic nanostructures have been widely studied due to their potential applicability into several research fields such as data storage, sensing and biomedical applications. Focusing on the biomedical aspect, some new approaches deserve to be mentioned: cell manipulation and separation, contrast-enhancing agents for magnetic resonance imaging, and magnetomechanically induced cell death. This work focuses on understanding three different magnetic nanostructures, disks in the vortex state, synthetic antiferromagnetic particles and nanowires, first, by explaining their interesting properties and how they behave under an applied external field, before reviewing their potential applications for each of the aforementioned techniques.The authors acknowledge funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie Grant Agreement No. 734801. C.R. and R.M. acknowledge funding from Basque Government Grant Nos. PIBA 2018-11 and IT1162-19, and Spanish Grant No. FIS2016-76058 (AEI/FEDER, UE). D.N. acknowledges the Spanish Ministry for Science, Innovation and Universities, for funding through the “Ramon y Cajal” program RYC-2017-22820. C.T. Sousa thanks FCT for financial support through the Investigador FCT program (Contract No. IF/01159/2015). R. Magalhães is grateful to the FCT SFRH/BD/148563/2019 PhD grant. This work was also supported by the Portuguese Fundação para a Ciência e a Tecnologia (FCT) and COMPETE 2020 (FEDER) under the projects POCI-01-0145-FEDER-028676/PTDC/CTM-CTM/28676/2017, POCI-01-0145/FEDER-032257/PTDC/FIS-OTI/32257/2017, POCI-01-0145-FEDER031302/PTDC/FIS-MAC/31302/2017, and POCI-01-0141-FEDER032527

Physico-chemical characterization of inclusion complex between hydroxymethylnitrofurazone and hydroxypropyl-beta-cyclodextrin

Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-beta-cyclodextrin (HP-beta-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-beta-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (deltaGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Physico-chemical characterization of inclusion complex between hydroxymethylnitrofurazone and hydroxypropyl-b-cyclodextrin

Hydroxymethylnitrofurazone (NFOH) is a prodrug that is active against Trypanosoma cruzi. It however presents low solubility and high toxicity. Hydroxypropyl-b-cyclodextrin (HP-b-CD) can be used as a drug-delivery system for NFOH modifying its physico-chemical properties. The aim of this work is to characterize the inclusion complex between NFOH and HP-b-CD. The rate of NFOH release decreases after complexation and thermodynamic parameters from the solubility isotherm studies revealed that a stable complex is formed (DGº= 1.7 kJ/mol). This study focuses on the physico-chemical characterization of a drug-delivery formulation that comes out as a potentially new therapeutic option for Chagas disease treatment312290295COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP00019-08-0305/03045-9; 04/02091-4; 06/00787-

AUTONOMIA NA VELHICE: CONCEPÇÕES DE IDOSOS PARTICIPANTES DE UM PROGRAMA DE AÇÃO SOCIAL

Neste estudo o GREG [1] propõe-se a identificar como os idosos do Programa PRÓ-MAIOR concebem a autonomia em suas vidas, considerando a contribuição da autonomia na qualidade de vida da pessoa idosa. Trata-se de uma pesquisa qualitativa exploratória, realizada através de entrevistas semiestruturadas, com oito idosos voluntários, que integram distintos grupos do Programa. Os dados analisados revelaram que autonomia relaciona-se com conhecimento, motivação, avaliação e capacidade decisória, que incluí a vontade de agir, ou seja, requer um comportamento proativo e que o exercício da autonomia relaciona-se com a saúde, a qualidade de vida e a independência financeira dos sujeitos de pesquisa. palavras-chave Envelhecimento Humano. Autonomia. Programa Social. [1] GREG - Grupo de Estudos Gerontológicos do Programa Maior Idade/PRÓ-MAIOR/Programa de Ação Social na Área do Envelhecimento Humano/Diretoria de Ação Social na Universidade do Vale do Rio dos Sinos – UNISINOS/RS. abstract In this study GREG proposes to identify how the elderly participants of the Program PRÓ-MAIOR conceive autonomy in their lives, considering the contribution of autonomy in the elderly quality of life. This is an exploratory qualitative research, conducted through semi-structured interviews with eight elderly volunteers that comprise distinct groups of the Program. The analysis showed that autonomy is related to knowledge, motivation, evaluation and decision capacity, which includes the will to act, that means, it requires a proactive behavior and that the exercise of autonomy is related to the health, the quality of life and the financial independence of the research subjects. keywords Human Aging. Autonomy. Social Program.

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Preparation, physicochemical characterization and stability evaluation of polymeric nanoparticles containing local anesthetics

Orientadores: Leonardo Fernandes Fraceto, Eneida de PaulaDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de BiologiaResumo: As principais características desejáveis para um anestésico local incluem longa duração de ação e baixa toxicidade sistêmica. Uma alternativa que tem se mostrado capaz de promover estes efeitos desejáveis é a liberação sustentada de fármacos através da veiculação destes em sistemas carreadores, como as nanopartículas. Nanopartículas poliméricas são sistemas carreadores que apresentam diâmetro inferior a 1µm e são classificadas como nanoesferas ou nanocápsulas. As nanocápsulas são constituídas por um invólucro polimérico disposto ao redor de um núcleo, geralmente oleoso, enquanto as nanoesferas são formadas somente por uma matriz polimérica. Os estágios iniciais do desenvolvimento de novas formulações contendo nanocarreadores de fármacos envolvem a otimização das condições de preparo, caracterização físico-química, avaliação da estabilidade e determinação do perfil de liberação do fármaco carreado, sendo esta a proposta desse trabalho. A otimização de formulações de nanocápsulas: a) de poli(ácido-lático-coácido- glicólico) contendo o anestésico local benzocaína; b) de poli (ácido lático-coglicólico) contendo bupivacaína e de c) de poli (e-caprolactona) contendo benzocaína, foi alcançada a partir de um planejamento fatorial, onde as propriedades avaliadas foram diâmetro das partículas, polidispersão, potencial zeta e eficiência de associação do fármaco nas nanocápsulas, em função de variações nas concentrações de polímero, óleo e tensoativos. Propriedades físicoquímicas das suspensões de nanocápsulas (das partículas, polidispersão, potencial zeta e eficiência de associação do fármaco) poliméricas foram avaliadas em função do tempo, a fim de determinar a estabilidade das formulações. Nenhuma das formulações estudadas apresentou grandes alterações dessas propriedades em função do tempo, sendo consideradas estáveis por um período de até 120 dias de armazenamento em temperatura ambiente. Foram obtidas nanocápsulas poliméricas de diâmetro, polidispersão, potencial zeta, eficiência de associação, perfil de liberação in vitro e estabilidade adequadas para a finalidade e via de administração infiltrativa. Os resultados apresentados são referentes a estudos iniciais do desenvolvimento dessas novas formulações visando reduzir a toxicidade, aumentar a solubilidade de anestésicos locais e abrem perspectivas para estudos pré-clínicos e clínicos, uma vez que se mostraram promissoresAbstract: Não informadoMestradoBioquimicaMestre em Biologia Funcional e Molecula