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Made available in DSpace on 2022-04-28T19:51:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 This study aimed to evaluate the effect of vitamin D deficiency on sleep quality, depression, anxiety, and physiological stress in patients with chronic obstructive pulmonary disease (COPD). We screened for COPD patients with normal (NorVD) (n=24) and insufficient (InsVD) (n=7) vitamin D levels. The Pittsburgh sleep quality index (PSQI), the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) and the Baevsky’s stress index were used for the sleep and psychometric evaluation. The evaluation of sleep quality by PSQI showed that NorVD individuals had higher duration and quality of sleep when compared with the InsVD group. Additionally, the group InsVD presented higher risk of developing sleep quality (OR=6.20; 95% CI=1.334, 29.013; p=0.009). BDI was higher in the InsVD, and this group had a higher risk of developing moderate and severe depression (OR=3.37; 95% CI=0.895, 12.722; p=0.03). The stress index indicated higher values in the InsVD in relation to the NorVD group (InsVD=24±0.8 vs. NorVD=16±0.9), and the group InsVD showed higher risk of developing high and very high physiological stress (OR=7.70; 95% CI=1.351, 43.878; p=0.01). The stress and sleep quality effects were negatively correlated with vitamin D levels. Insufficient levels of vitamin D negatively affect sleep quality and psychometric variables. Universidade Federal do Maranhão Departamento de Educação Física, MA Universidade Estadual de São Paulo Departamento de Farmácia, São Paulo Universidade Federal de São Paulo Departamento de Psicobiologia, São Paulo Universidade Federal do Maranhão Departamento de Medicina, MA Universidade Estadual de Campinas Departamento de Educação Física, São Paulo Universidade Estadual de São Paulo Departamento de Farmácia, São Paulo

Made available in DSpace on 2022-05-01T15:46:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-25 Glioblastoma multiforme (GBM) is the most common malignant brain cancer, characterized by high invasiveness and poor prognosis. Docetaxel (DTX) is a chemotherapeutic drug with promising anti-tumor properties. However, conventional intravenous formulations exhibit side effects of systemic biodistribution and low brain bioavailability, limiting their clinical use. The current work aimed to evaluate the effect of DTX-loaded nanostructured lipid carriers (NLC) functionalized with bevacizumab (BVZ-NLC-DTX) against GBM using in vitro and in vivo models. The NLC was obtained by the fusion-emulsification method followed by sonication, with narrow size distribution, negative zeta potential, and low polydispersity index. NLC showed DTX entrapment efficiency above 90%. BVZ coupling efficiency was 62% and BVZ integrity after functionalization was confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Calorimetry studies confirmed thermal stability and molecular dispersion of DTX in the lipid matrix. NLC showed a sustained DTX release over 84 h. In vitro anti-tumor assays shown that BVZ-NLC-DTX selectively increased the cytotoxic of DTX in cells overexpressing VEGF (U87MG and A172), but not in peripheral blood mononuclear cells (PMBCs), promoting cell death by apoptosis. BVZ functionalization did not impair cellular uptake. An in vivo orthotopic rat model demonstrated that free-DTX was not capable of reducing tumor growth whereas BVZ-NLC-DTX reduced up to 70% tumor volume after 15-days of treatment. Therefore, this study contributes to understanding new nanotechnology-based vehicles capable of reaching the brain more efficiently and repurposing the use of anti-cancer drugs in GBM treatment. School of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo Hematology and Transfusion Medicine Center University of Campinas School of Pharmaceutical Science of Ribeirão Preto University of São Paulo (USP), São Paulo chool of Dentistry São Paulo State University (UNESP), São Paulo School of Pharmaceutical Sciences São Paulo State University (UNESP), São Paulo chool of Dentistry São Paulo State University (UNESP), São Paulo