DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item Seasonality study of essential oil from leaves of Cymbopogon densiflorus and nanoemulsion development with antioxidant activity.(2019) Seibert, Janaína Brandão; Rodrigues, Ivanildes Vasconcelos; Carneiro, Simone Pinto; Amparo, Tatiane Roquete; Lanza, Juliane Sousa; Frezard, Frederic Jean Georges; Souza, Gustavo Henrique Bianco de; Santos, Orlando David Henrique dosThe development of formulations that maintain the biological and physical chemistry properties of essential oils is an important choice when they are used as an active ingredient. This study aimed to characterize the essential oil from leaves of Cymbopogon densiflorus and evaluate the antioxidant activity of the oil, and to produce a nanoemulsion formulation containing it. The essential oil was obtained by hydrodistillation, and seasonality was analysed every 2 months by gas chromatography–mass spectrometry, showing that more than 90% of the composition was maintained for the whole period and that the major compounds were trans‐p‐menta‐2,8‐dien‐1‐ol, cis‐p‐menta‐2,8‐dien‐1‐ol, trans‐p‐menta‐1(7),8‐dien‐2‐ol, cis‐piperitol, and cis‐p‐menta‐1(7),8‐dien‐2‐ol. Stable nanoemulsions were prepared by phase inversion method encapsulating the essential oil. The antioxidant activity was evaluated by 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) free radical scavenging and 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid (ABTS) methods. In the first test, free and nanoemulsified essential oil showed half‐maximal inhibitory concentration (IC50) values equivalent to 14.689 and 3.692 mg mL−1, respectively. In the second test, these values were 0.567 and 0.43 mg mL−1. The development of nanoemulsion‐based essential oil from leaves of C. densiflorus was viable, and the formulated oil was able to reproduce the antioxidant activity at a concentration four times lower than that of the pure essential oil.Item Association of water extract of green propolis and liposomal meglumine antimoniate in the treatment of experimental visceral leishmaniasis.(2014) Ferreira, Flávia Monteiro; Castro, Renata Alves de Oliveira e; Batista, Maurício Azevedo; Rossi, Fernanda Mendes de Oliveira; Lemos, Denise da Silveira; Frezard, Frederic Jean Georges; Moura, Sandra Aparecida Lima de; Rezende, Simone AparecidaThis work investigated the use of water extract of green propolis (WEP) and its association with free or liposomal meglumine antimoniate (MA) for the treatment of murine visceral leishmaniasis. Mice infected with Leishmania infantum were treated with oral doses of WEP associated or not with a single dose of liposomal MA by intraperitoneal route. Parasite burden was assessed in the liver and spleen by limiting dilution assay, and alterations in the spleen cellular phenotype were evaluated by flow cytometry. Tissue damage was assessed by determination of biochemical markers of the liver, heart, and kidney function and histopathological analysis of the liver and spleen. Our data showed that treatmentwith WEP was able to reduce parasite load in the liver but not in the spleen. On the other hand, liposomal MA reduced parasite load in both organs. Unexpectedly, there was no synergism with the combination of WEP and liposomal MA in reducing the parasite load. The histopathological analysis showed that administration of WEP, liposomal MA, or their association was able to protect the liver and spleen fromlesions caused by infection. No alteration in the profile of spleen cells by flow cytometry or in the liver, heart, and kidney functions by biochemical markers due to any of the treatments was observed. These results demonstrate that althoughWEP was able to significantly reduce the liver parasite load, its association with liposomalMA did not lead to significant improvement in reducing parasite load. On the other hand, treatment with WEP and/or liposomal MA protected the liver and spleen from lesions caused by the infection.Item Long-lasting cardiovascular effects of liposomes-entrapped angiotensin-(1-7) at the rostral ventrolateral medulla.(2001) Barcellos, Neila Marcia Silva; Frezard, Frederic Jean Georges; Caligiorne, Sordaini Maria; Santos, Robson Augusto Souza dosThe aim of this work was to evaluate the potential of liposomes as a tool for the sustained release of the short half-life peptides of the renin-angiotensin system in a specific site of the brain. Angiotensin (Ang)-(1-7) was selected for this study because of its known cardiovascular effects at the level of the rostral ventrolateral medulla (RVLM) and because of the considerable interests in elucidating its physiopathological role as a neuromodulator. Ang-(1-7)– containing liposomes (LAng) were microinjected unilaterally in the RVLM of Wistar rats, and the effects on blood pressure (MAP) and heart rate were evaluated by telemetry. Empty liposomes (Lemp) were used as control. LAng elicited a significant pressor effect during daytime and bradycardia during nighttime that lasted for 5 and 3 days, respectively. These cardiovascular effects resulted in a significant attenuation of the circadian variations of MAP and heart rate. In the case of MAP, a significant inversion of the circadian rhythm was observed on day 2 after LAng microinjection. None of these effects were observed following microinjection of Lemp. Using this novel technique, it was possible to establish, in chronic conditions, the pressor effect of Ang-(1-7) at the RVLM. Moreover, our data unmasks a new physiological role for Ang-(1-7) at the level of the RVLM: modulation of the circadian rhythms of MAP and heart rate.Item Hepatotoxicity of pentavalent antimonial drug : possible role of residual Sb(III) and protective effect of ascorbic acid.(2013) Kato, Kelly Cristina; Teixeira, Eliane Morais; Reis, Priscila Gomes dos; Barcellos, Neila Marcia Silva; Salaün, Pascal; Campos, Paula Peixoto; Corrêa Junior, José Dias; Rabello, Ana Lúcia Teles; Demicheli, Cynthia Peres; Frezard, Frederic Jean GeorgesPentavalent antimonial drugs such as meglumine antimoniate (Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including cardiotoxicity and hepatotoxicity, during the treatment of leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of meglumine antimoniate, as well as the protective effect of the antioxidant ascorbic acid (AA) during antimonial chemotherapy in a murine model of visceral leishmaniasis. BALB/c mice infected with Leishmania infantum were treated intraperitoneally at 80 mg of Sb/kg/day with commercial meglumine antimoniate (Glu) or a synthetic meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations, peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial therapy.Item Enhanced schistosomicidal efficacy of tartar emetic encapsulated in pegylated liposomes.(2003) Melo, Alan Lane de; Barcellos, Neila Marcia Silva; Demicheli, Cynthia Peres; Frezard, Frederic Jean GeorgesThe aim of the present study was to evaluate the ability of liposomes to improve the efficacy of tartar emetic (TA) against established Schistosoma mansoni infection. TA was used as a schistosomicidal drug model and both conventional liposomes (CL) and long-circulating pegylated liposomes (LCL) were evaluated. In the first experiment, TA, either free or encapsulated within CL or LCL, was given intraperitoneally (i.p.) as a single dose of 11 mg Sb/kg to mice experimentally infected with S. mansoni. Only the group treated with LCL showed a significant (55%) reduction in the worm burden, compared to the control groups (untreated or treated with empty LCL). In the second experiment, the efficacy of TA-containing LCL was evaluated at a higher dose (27 mg Sb/kg) by both subcutaneous (s.c.) and i.p. routes. Reduction levels of 67 and 82% were achieved by s.c. and i.p. routes, respectively. Strikingly, all mice survived to this high dose of antimony. This is in contrast with free TA that was lethal in 100% of mice at the same dose. The present work demonstrates that LCL reduce the acute toxicity of TA and effectively deliver this drug to S. mansoni during the late stages of parasite infection.Item A novel approach based on nanotechnology for investigating the chronic actions of short-lived peptides in specific sites of the brain.(2007) Frezard, Frederic Jean Georges; Barcellos, Neila Marcia Silva; Santos, Robson Augusto Souza dosThis review presents a novel experimental approach for investigating the chronic actions of short-lived peptides in specific sites of the brain. This method combines the advantages of three different techniques: liposome encapsulation, site-specific microinjection and telemetry. First, liposomes can be designed to remain located at the injection site for a long period of time, where they protect encapsulated peptide from rapid degradation and act as a sustained-release system. Secondly, microinjection allows the administration of peptides in specific sites of the brain with minimal side effects. Finally, using telemetry, it is possible to register physiological parameters and their circadian variations in undisturbed freemoving animals for several days. Angiotensin-(1–7) and angiotensin II were used as peptide models, in order to validate the proposed method. Following the unilateral microinjection of the liposome-encapsulated peptides into the rostral ventrolateral medulla (RVLM) of Wistar rats, longlasting cardiovascular actions were elicited, for several days. Importantly, new physiological actions of angiotensin-(1–7) at the RVLM were unmasked: modulation of the circadian rhythms of blood pressure and heart rate. It is felt that this method can be applied to a wide variety of shortlived bioactive peptides and should encounter numerous applications in the field of neurosciences.Item Site-specific microinjection of liposomes into the brain for local infusion of a short-lived peptide.(2004) Barcellos, Neila Marcia Silva; Caligiorne, Sordaini Maria; Santos, Robson Augusto Souza dos; Frezard, Frederic Jean GeorgesThe short-lived peptide, angiotensin-(1-7) (Ang-(1-7)), was encapsulated in different liposome preparations, in order to evaluate the influence of membrane fluidity, membrane surface, liposome size and dose of peptide on the cardiovascular effects of the encapsulated peptide at a specific site of the brain. These preparations were microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of Wistar rats, and mean arterial blood pressure (MAP) and heart rate (HR) were registered by telemetry. Pegylated, rigid and calibrated (200 nm) liposomes, containing 50 ng of Ang-(1-7), elicited a significant increase of MAP for at least 7 days, in contrast to empty liposomes or non-pegylated liposomes. When a two-fold higher peptide dose was employed or when pegylated liposomes were used in the fluid state or uncalibrated, less pronounced pressor effects were observed. These data show that the cardiovascular responses to the microinjection of Ang-(1-7)- containing liposomes into the RVLM can be modulated through the manipulation of liposome characteristics. These results can be explained by the influence of liposome characteristics on the flux of peptide release. It is expected that this new method will encounter numerous applications in the study of the chronic actions of short-lived bioactive peptides in specific sites of the brain.Item Reduced cardiovascular alterations of tartar emetic administered in long-circulating liposomes in rats.(2010) Maciel, Naira Rezende; Reis, Priscila Gomes dos; Kato, Kelly Cristina; Vidal, Alessandra Teixeira; Guimarães, Homero Nogueira; Frezard, Frederic Jean Georges; Barcellos, Neila Marcia Silva; Guimarães, Andrea GrabeTrivalent antimonial drugs, including tartar emetic (TA), are known to induce important cardiotoxicity observed by electrocardiographic abnormalities. Liposome encapsulation was found to reduce the overall acute toxicity of TA. The present work investigated the cardiovascular parameters alterations of rats submitted to the treatment with free and encapsulated TA in long-circulating liposomes. Liposomes were made using lipids DSPC, DSPE-PEG and cholesterol. The cardiovascular signals, electrocardiogram (ECG) and arterial blood pressure (AP), were recorded from anaesthetized Wistar rats after intravenous (IV) administration of a single specially high dose (17 mg/kg) of TA in liposomes and in free form. The IV administration of TA solution caused significant increase of QT interval of ECG and significant reduction of AP when compared to the control group. These alterations were not observed when liposomes TA were administered and the profile of ECG and AP data was quite similar to the control groups. In conclusion, a liposomal formulation of TA showed a reduced cardiotoxic profile for TA when compared to the free form.Item Prolonged cardioprotective effect of pyridostigmine encapsulated in liposomes.(2010) Vidal, Alessandra Teixeira; Guimarães, Homero Nogueira; Paula, Danielle Cristiane Correa de; Frezard, Frederic Jean Georges; Barcellos, Neila Marcia Silva; Guimarães, Andrea GrabeAims: The purpose of the present work was to investigate the ability of pyridostigmine encapsulated in longcirculating liposomes, to protect against ECG(electrocardiogram) alterations induced by sympathetic stimulation in rats. Main methods: The encapsulation of pyridostigmine was carried out by freeze–thaw and extrusion. Blood pressure and ECG (limb lead II) were monitored in anaesthetized male Wistar rats. The formulation containing pyridostigmine was intravenously administrated in 0.1, 0.3 and 1.0 mg/kg doses, and sympathetic stimulation was conducted by administration of 1 or 3 μg of noradrenaline (NA) after 1, 2, 4 or 6 h. The obtained cardiovascular parameters were compared to animals that received intravenous injection of pyridostigmine in free form or saline. Key findings: After saline, NA induced a significant increase in QT interval (22.3% after 3.0 μg). Previous administration of free pyridostigmine significantly prevented the increase of QT interval after sympathetic stimulation and the most prominent effect was observed after 1h for the dose of 0.3 mg/kg (6.8% after 3.0 μg of NA) and was no longer observed after 2 h of the treatment. On the other hand, the maximum effect of pyridostigmine in liposomal formulation preventing QT interval increasewas observed 2 h after treatment (9.7% after 3.0 μg of NA) and was still present until 6 h when 1 mg/kg was previous administrated. Significance: The results of the present study, beyond to confirm the cardioprotective action of pyridostigmine, suggest that liposomal pyridostigmine may be a potential therapeutic alternative to prevent cardiovascular disturbances resulting from sympathetic hyperactivity.