DEFAR - Artigos publicados em periódicos
URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531
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Item Lecithin-based nanocapsule loading sucupira (Pterodon emarginatus) oil effects in experimental mucositis.(2022) Di Miceli, Jeruza Ferraz Filgueiras; Andrade, Maria Emília Rabelo; Carvalho, Paula Lopes Armond; Santos, Elandia Aparecida; Oliveira, Anna Eliza Maciel de Faria Mota; Fernandes, Caio Pinho; Cruz, Rodrigo Alves Soares; Garrett, Rafael; Mosqueira, Vanessa Carla Furtado; Cassali, Geovanni Dantas; D’Haese, Cecile; Nysten, Bernard; Leite, Jacqueline Isaura Alvarez; Cardoso, Valbert Nascimento; Araújo, Raquel SilvaIntestinal mucositis (IM) is a frequent adverse effect in anticancer therapy without standard treatment. The oil obtained from sucupira (Pterodon emarginatus) has anti-inflammatory properties, and the soybean lecithin re- duces the intestinal toxicity of several xenobiotics. However, their water insolubility impairs the in vivo appli- cation. For this reason, we evaluated if the nanoencapsulation of sucupira oil (SO) in lecithin-based nanocapsules (SO-NC) could be a therapeutically effective system for the treatment of IM in murine cisplatin (CDDP)-induced intestinal mucositis model. SO was analyzed by LC-HRMS/MS and HPLC. SO-NC was prepared by nano- precipitation and characterized using DLS, HPLC, and AFM. Mice body weight and food consumption were assessed daily during experimental mucositis induced by CDDP. The animals were euthanized, and intestinal permeability, inflammatory mediators, and intestinal histology were performed. SO-NC demonstrated adequate characteristics for oral administration as size under 300 nm, IP < 0.3, high EE, and spherical shape. In vitro cytotoxicity performed against RAW 264.7 cell lines resulted in cell viability above 80 % confirming the non- cytotoxic profile of SO (IC50 268 μg/mL) and SO-NC (IC50 118.5 μg/mL) up to 117.2 μg/mL. The untreated mice showed intestinal toxicity after i.p. of CDDP, principally weight loss, increased intestinal permeability, and MPO and TNF-α levels. Surprisingly, the administration of SO to CDDP-mucositis animals did not circumvent the CDDP effects and increased intestinal permeability. However, SO-NC proved efficient in mitigating the experi- mental intestinal mucositis by improving intestinal epithelium architecture, reducing intestinal permeability, and improving the MPO levels. In conclusion, SO-NC can positively impact intestinal mucositis by promoting mucosal recovery. This is a promising strategy for developing a new treatment for intestinal mucositis.Item Chemical characterization and anti-inflammatory assessment of the hydroethanolic extract of Fridericia chica.(2020) Takenaka, Isabella Kuniko Tavares Magalhães; Amorim, Juliana Mendes; Barros, Patrícia Aparecida Vieira de; Brandão, Geraldo Célio; Contarini, Sara Moreira Lopes; Melo, Éricka Lorenna de Sales Souza e; Leite, Camila Megale Almeida; Martins, Flaviano dos Santos; Cardoso, Valbert Nascimento; Castilho, Rachel Oliveira; Diniz, Simone Odília Antunes FernandesFridericia chica (Bonpl.) L.G. Lohmann, Bignoniaceae, is an Amazonian species known as “pariri” or “crajiru” that is included in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (Renisus). This herbal remedy is traditionally used as an infusion to treat diarrhea, anemia, inflammation, symptoms of mucositis, and frequent complications of chemotherapy. This study aimed to characterize the chemical profile of the hydroethanolic extract of F. chica and to assess its intestinal anti-inflammatory activity. The chemical profile of the leaves was determined by ultra-performance liquid chromatog raphy coupled to mass spectrometry, and its potential anti-inflammatory activity in the gut was evaluated in mucositis induced by 5-fluorouracil. Three novel compounds from this the species were identified 6,7,3′,4′-tetrahydroxy-5-methoxyflavilium-O-glu curonide, scutellarein-O-glucuronide, and 5-methyl-scutellarein-O-glucuronide, as well as flavones and anthocyanidins that have been previously described. Mice received the hydroethanolic extract (300 mg/kg) for 9 days, and no signs of toxicity were observed. After 72 h of 5-fluorouracil administration, intestinal permeability, bacterial translocation, myeloperoxidase activity, eosinophil peroxidase activity, and histological analyses were performed. Treatment with the analyzed extract was beneficial, as it normalized intestinal permeability, bacterial translocation, myeloperoxidase activity/eosinophil peroxidase and preserved intestinal epithelium architecture. This study provides new insights into the chemical composition and biological activity of the polar extracts from “pariri”, an important Amazonian crude medicinal drug.Item Toxicological study of a new doxorubicin-loaded pH-sensitive liposome : a preclinical approach.(2018) Silva, Juliana de Oliveira; Miranda, Sued Eustaquio Mendes; Leite, Elaine Amaral; Sabino, Adriano de Paula; Borges, Karina Braga Gomes; Cardoso, Valbert Nascimento; Cassali, Geovanni Dantas; Guimarães, Andrea Grabe; Oliveira, Mônica Cristina de; Barros, André Luís Branco deDoxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies. Therefore, the aim of this work was to investigate the acute toxicity and cardiotoxicity of DOX-loading pH-sensitive liposomes (SpHL-DOX). To achieve this, female BALB/c mice, after intravenous administration, were monitored by means of clinical, laboratory, histopathological and electrocardiographic (ECG) analyses. Results indicate that SpHL was able to prevent renal toxicity and the hepatic injury was less extensive than free DOX. In addition, lower body weight loss was associated with less ECG QT interval prolongation to animals receiving SpHL-DOX (14.6 ± 5.2%) compared to animals receiving free DOX (35.7 ± 4.0%) or non-pH-sensitive liposomes (nSpHL-DOX) (47.0 ± 9.8%). These results corroborate with SpHL-DOX biodistribution studies published by our group. In conclusion, the SpHL-DOX showed less toxic effects on mice compared to free DOX or nSpHL-DOX indicating that SpHL-DOX is a promising strategy to reduce the serious cardiotoxic effects of DOX.Item Biodistribution of free and encapsulated 99mTc-fluconazole in an infection model induced by Candida albicans.(2018) Assis, Danielle Nogueira de; Araújo, Raquel Silva; Fuscaldi, Leonardo Lima; Diniz, Simone Odília Antunes Fernandes; Mosqueira, Vanessa Carla Furtado; Cardoso, Valbert NascimentoCandida spp is an etiologic agent of fungal infections in hospitals and resistance to treatment with antifungals has been extensively reported. Thus, it is very important to develop formulations that increase effectiveness with low toxicity. In this sense, nanocarriers have been investigated, once they modify drug biodistribution profile. Thus, this study aimed to evaluate the biodistribution of free and encapsulated 99mTc-fluconazole into nanocapsules (NCs) in an experimental immunosuppressed murine model of Candida albicans infection.Item Nitric oxide-induced vasorelaxation in response to PnTx2-6 toxin from Phoneutria nigriventer spider in rat cavernosal tissue.(2010) Nunes, Kenia Pedrosa; Cordeiro, Marta do Nascimento; Richardson, Michael; Borges, Marcia Helena; Diniz, Simone Odília Antunes Fernandes; Cardoso, Valbert Nascimento; Passaglia, Rita de Cassia Aleixo Tostes; Garcia, Maria Elena de Lima Perez; Webb, Robert Clinton; Leite, RomuloIntroduction—Priapism is one of several symptoms observed in accidental bites by the spider Phoneutria nigriventer. The venom of this spider is comprised of many toxins, and the majority has been shown to affect excitable ion channels, mainly sodium (Na+) channels. It has been demonstrated that PnTx2-6, a peptide extracted from the venom of P. nigriventer, causes erection in anesthetized rats and mice. Aim—We investigated the mechanism by which PnTx2-6 evokes relaxation in rat corpus cavernosum. Main Outcome Measures—PnTx2-6 toxin potentiates nitric oxide (NO)-dependent cavernosal relaxation.Item PLA-PEG nanocapsules radiolabeled with 99mTechnetium-HMPAO : release properties and physicochemical characterization by atomic force microscopy and photon correlation spectroscopy.(2008) Pereira, Maira Alves; Mosqueira, Vanessa Carla Furtado; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Ramaldes, Gilson Andrade; Cardoso, Valbert NascimentoThe present work describes the preparation, characterization and labelling of conventional and surface-modified nanocapsules (NC) with 99mTc-HMPAO. The size, size distribution and homogeneity were determined by photon correlation spectroscopy (PCS) and zeta potential by laser doppler anemometry. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The stability and release profile of the NC were determined in vitro in plasma. The results showed that the use of methylene blue induces significant increase in the encapsulation efficiency of 99mTc-HMPAO, from 24.4 to 49.8% in PLANC and 22.37 to 52.93% in the case of PLA-PEGNC(P < 0.05) by improving the complex stabilization. The average diameter of NC calculated by PCS varied from 216 to 323 nm, while the average diameter determined by AFM varied from 238 to 426 nm. The AFM analysis of diameter/height ratios suggested a greater homogeneity of the surface-modified PLAPEG nanocapsules compared to PLA NC concerning their flattening properties. The in vitro release of the 99mTc-HMPAO in plasma medium was faster for the conventional PLA NC than for the surface-modified NC. For the latter, 60% of the radioactivity remained associated with NC, even after 12h of incubation. The results suggest that the surface-modified 99mTc-HMPAO-PLA PEG NCwas more stable against label leakage in the presence of proteins and could present better performance as radiotracer in vivo.Item Release profiles and morphological characterization by atomic force microscopy and photon correlation spectroscopy of 99mTechnetium-fluconazole nanocapsules.(2008) Assis, Danielle Nogueira de; Mosqueira, Vanessa Carla Furtado; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Cardoso, Valbert NascimentoSeveral classes of antifungal have been employed in candidiasis treatment, but patients with advanced immunodeficiency can present unsatisfactory results after therapy. In these cases, high doses of drugs or the use of multiple agents are sometimes used, and hence increasing the risk of serious side effects. Considering theses difficulties, the encapsulation of antifungal agents in nanoparticulate carriers has been used with the objective of modifying the pharmacokinetic of drugs resulting in more efficient treatments with less side effects. The purpose of this work was the preparation, characterization and the investigation of the release profiles of radiolabeled fluconazole nanocapsules. The size, homogeneity and zeta potential of NC preparations were determined with a Zetasizer 3000HS. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The release study in vitro of NC was evaluated in physiologic solution with or without 70% mouse plasma. The labeling yield of fluconazole with 99mTc was 94% and the radiolabeled drug was stable within 24 h period. The encapsulation percentage of 99mTc-fluconazole in PLA-POLOX NC and PLA-PEG NC was approximately of 30%. The average diameter calculated by photon correlation spectroscopy (PCS) varied from 236 to 356 nm, while the average diameter determined by AFM varied from 238 to 411 nm. The diameter/height relation decreased significantly when 25% glutaraldehyde was used for NC fixation on mica. The zeta potential varied from −55 to −69 nm and surface-modified NC showed lower absolute values than conventional NC. The in vitro release of 99mTc-fluconazole in plasma medium of the conventional and surface-modified NC was greater than in saline. The drug release in plasma medium from conventional NC was faster than for surface-modified NC. The results obtained in this work suggest that the nanocapsules containing fluconazole could be used to identify infectious foci, due to the properties, such as size, zeta potential and controlled release of 99mTc-fluconazole. The surface-modified nanocapsules could constitute a long-circulating intravenous formulation of fluconazole for treating sepsis caused by disseminated form of candidiasis. However, in vivo studies should be considered and are under investigation.