DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item Polyester nanocapsules for intravenous delivery of artemether : formulation development, antimalarial efficacy, and cardioprotective effects in vivo.(2022) Diniz, Alessandra Teixeira Vidal; Guimarães, Homero Nogueira; Garcia, Giani Martins; Braga, Érika Martins; Richard, Sylvain; Guimarães, Andrea Grabe; Mosqueira, Vanessa Carla FurtadoArtemether (ATM) is an effective antimalarial drug that also has a short half-life in the blood. Furthermore, ATM is also cardiotoxic and is associated with pro-arrhythmogenic risks. We aimed to develop a delivery system enabling the prolonged release of ATM into the blood coupled with reduced cardiotoxicity. To achieve this, we prepared polymeric nanocapsules (NCs) from different biodegradable polyesters, namely poly(D,L-lactide) (PLA), poly-ε-caprolactone (PCL), and surface-modified NCs, using a monomethoxi-polyethylene glycol-block-poly(D,L-lactide) (PEG5kDa- PLA45kDa) polymer. Using this approach, we were able to encapsulate high yields of ATM (>85%, 0–4 mg/mL) within the oily core of the NCs. The PCL-NCs exhibited the highest percentage of ATM loading as well as a slow release rate. Atomic force microscopy showed nanometric and spherical particles with a narrow size dispersion. We used the PCL NCs loaded with ATM for biological evaluation following IV administration. As with free-ATM, the ATM-PCL-NCs formulation exhibited potent antimalarial efficacy using either the “Four-day test” protocol (ATM total at the end of the 4 daily doses: 40 and 80 mg/kg) in Swiss mice infected with P. berghei or a single low dose (20 mg/kg) of ATM in mice with higher parasitemia (15%). In healthy rats, IV administration of single doses of free-ATM (40 or 80 mg/kg) prolonged cardiac QT and QTc intervals and induced both bradycardia and hypotension. Repeated IV administration of free-ATM (four IV doses at 20 mg/kg every 12 h for 48 h) also prolonged the QT and QTc intervals but, paradoxically, induced tachycardia and hypertension. Remarkably, the incorporation of ATM in ATM-PCL-NCs reduced all adverse effects. In conclusion, the encapsulation of ATM in biodegradable polyester NCs reduces its cardiovascular toxicity without affecting its antimalarial efficacy.Item Bioprospection for antiplasmodial activity, and identification of bioactive metabolites of native plants species from the Mata Atlântica biome, Brazil.(2019) Gontijo, Douglas da Costa; Leite, João Paulo Viana; Nascimento, Maria Fernanda Alves do; Brandão, Geraldo Célio; Oliveira, Alaíde Braga deA total of 33 extracts of eleven different plants species from Mata Atlântica biome, Brazil, and different fractions of the bioactive extracts were evaluated against chloroquine-resistant Plasmodium falciparum W2 strain by PfLDH method and cytotoxicity to HepG2 cells by the MTT assay, and chemically characterized by LC-DAD-ESI-MS/MS analysis. The results allowed the identification of Alchornea glandulosa, Miconia latecrenata, and Psychotria suterella as the most active plant species. Different flavonoids and tannins in Alchornea glandulosa and Miconia latecrenata besides alkaloids in Psychotria suterella were identified. Bioguided fractionation of A. glandulosa and M. latecrenata leaves extracts led to fractions exhibiting high parasite growth inhibition. Seven known alkaloids were identified in the P. suterella extract, and of these, only 5-carboxystrictosidine had been assayed for antiplasmodial activity what points to this species as the most promising among the eleven one assayed.Item Reduced cardiotoxicity and increased oral efficacy of artemether polymeric nanocapsules in Plasmodium berghei-infected mice.(2018) Souza, Ana Carolina Moreira; Mosqueira, Vanessa Carla Furtado; Silveira, Ana Paula Amariz; Antunes, Lidiane Rodrigues; Richard, Sylvain; Guimarães, Homero Nogueira; Guimarães, Andrea GrabeArtemether (ATM) cardiotoxicity, its short half-life and low oral bioavailability are the major limiting factors for its use to treat malaria. The purposes of this work were to study free-ATM and ATM-loaded poly-ε-caprolactone nanocapules (ATM-NC) cardiotoxicity and oral efficacy on Plasmodium berghei-infected mice. ATM-NC was obtained by interfacial polymer deposition and ATM was associated with polymeric NC oily core. For cardiotoxicity evaluation, male black C57BL6 uninfected or P. berghei-infected mice received, by oral route twice daily/4 days, vehicle (sorbitol/carboxymethylcellulose), blank-NC, free-ATM or ATMNC at doses 40, 80 or 120 mg kg−1 . Electrocardiogram (ECG) lead II signal was obtained before and after treatment. For ATM efficacy evaluation, female P. berghei-infected mice were treated the same way. ATM-NC improved antimalarial in vivo efficacy and reduced mice mortality. Free-ATM induced significantly QT and QTc intervals prolongation. ATMNC (120 mg kg−1 ) given to uninfected mice reduced QT and QTc intervals prolongation 34 and 30%, respectively, compared with free-ATM. ATM-NC given to infected mice also reduced QT and QTc intervals prolongation, 28 and 27%, respectively. For the first time, the study showed a nanocarrier reducing cardiotoxicity of ATM given by oral route and it was more effective against P. berghei than free-ATM as monotherapy.Item Anti-malarial activity and toxicity assessment of Himatanthus articulatus, a plant used to treat malaria in the Brazilian Amazon.(2015) Vale, Valdicley Vieira; Vilhena, Thyago da Costa; Trindade, Rafaela Cabral dos Santos; Ferreira, Marlia Regina Coelho; Percário, Sandro; Soares, Luciana Ferreira; Pereira, Washington Luiz Assunção; Brandão, Geraldo Célio; Oliveira, Alaíde Braga de; Dolabela, Maria Fâni; Vasconcelos, Flávio deBackground: Plasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus. Methods: Ethanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulates and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity - TEAC; lipid peroxidation – TBARS, and nitrites and nitrates - NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice. Results: Plumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies. Conclusions: The ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.Item Nanotechnology applied to the treatment of malaria.(2010) Magalhães, Nereide Stela Santos; Mosqueira, Vanessa Carla FurtadoDespite the fact that we live in an era of advanced technology and innovation, infectious diseases, like malaria, continue to be one of the greatest health challenges worldwide. The main drawbacks of conventional malaria chemotherapy are the development of multiple drug resistance and the non-specific targeting to intracellular parasites, resulting in high dose requirements and subsequent intolerable toxicity. Nanosized carriers have been receiving special attention with the aim of minimizing the side effects of drug therapy, such as poor bioavailability and the selectivity of drugs. Several nanosized delivery systems have already proved their effectiveness in animal models for the treatment and prophylaxis of malaria. A number of strategies to deliver antimalarials using nanocarriers and the mechanisms that facilitate their targeting to Plasmodium spp.-infected cells are discussed in this review. Taking into account the peculiarities of malaria parasites, the focus is placed particularly on lipid-based (e.g., liposomes, solid lipid nanoparticles and nano and microemulsions) and polymer-based nanocarriers (nanocapsules and nanospheres). This review emphasizes the main requirements for developing new nanotechnology-based carriers as a promising choice in malaria treatment, especially in the case of severe cerebral malaria.