DEFAR - Artigos publicados em periódicos
URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531
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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.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 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.