DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Resultados da Pesquisa
Item Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis.(2021) Kawakami, Monique Yoko Martins; Zamora, Lisset Ortiz; Araújo, Raquel Silva; Fernandes, Caio Pinho; Ricotta, Tiago Queiroga Nery; Oliveira, Leandro G. de; Queiroz Júnior, Celso Martins; Fernandes, Ana Paula Salles Moura; Conceição, Edemilson Cardoso da; Ferreira, Lucas Antônio Miranda; Barros, André Luís Branco de; Aguiar, Marta Marques Gontijo de; Oliveira, Anna Eliza Maciel de Faria MotaCutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resis- tance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intra- peritoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histo- pathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.Item Recent progress in micro and nano-encapsulation of bioactive derivatives of the Brazilian genus Pterodon.(2021) Lemos, Janaina de Alcantara; Oliveira, Anna Eliza M. F. M.; Araújo, Raquel Silva; Townsend, Danyelle M.; Ferreira, Lucas Antônio Miranda; Barros, André Luís Branco deIn the last few decades, utilization of medicinal plants by the pharmaceutical industry has led to the identifi- cation of many new bioactive compounds. The genus Pterodon, native of the Brazilian Flora, is known for the therapeutic properties attributed to its species, which are widely used in popular medicine for their anti- inflammatory, anti-rheumatic, tonic, and depurative properties. The intrinsic low water solubility of the plant derivatives from the genus, including diterpenes with vouacapane skeletons that are partially associated with the pharmacological activities, impairs the bioavailability of these bioactive compounds. Recent studies have aimed to encapsulate Pterodon products to improve their water solubility, achieve stability, increase their efficacy, and allow clinical applications. The purpose of this paper is to review recent research on the use of nanotechnology for the development of new products from plant derivatives of the Pterodon genus in different types of micro- and nanocarriers. Therapeutic properties of their different products are also presented. Finally, an update about the current and future applications of encapsulated formulations is provided.Item Mechanistic insights into the intracellular release of doxorubicin from pH-sensitive liposomes.(2021) Reis, Samara Bonesso dos; Silva, Juliana de Oliveira; Fossa, Fernanda Garcia; Leite, Elaine Amaral; Souza, Angelo Malachias de; Lana, Gwenaelle Elza Nathalie Pound; Mosqueira, Vanessa Carla Furtado; Oliveira, Mônica Cristina de; Barros, André Luís Branco de; Jesus, Marcelo Bispo depH-sensitive liposomes are interesting carriers for drug-delivery, undertaking rapid bilayer destabilization in response to pH changes, allied to tumor accumulation, a desirable behavior in the treatment of cancer cells. Previously, we have shown that pH-sensitive liposomes accumulate in tumor tissues of mice, in which an acidic environment accelerates drug delivery. Ultimately, these formulations can be internalized by tumor cells and take the endosome-lysosomal route. However, the mechanism of doxorubicin release and intracellular traffic of pH-sensitive liposomes remains unclear. To investigate the molecular mechanisms underlying the intracellular release of doxorubicin from pH-sensitive liposomes, we followed HeLa cells viability, internalization, intracel lular trafficking, and doxorubicin’s intracellular delivery mechanisms from pH-sensitive (SpHL-DOX) and non pH-sensitive (nSpHL-DOX) formulations. We found that SpHL-DOX has faster internalization kinetics and intracellular release of doxorubicin, followed by strong nuclear accumulation compared to nSpHL-DOX. The increased nuclear accumulation led to the activation of cleaved caspase-3, which efficiently induced apoptosis. Remarkably, we found that chloroquine and E64d enhanced the cytotoxicity of SpHL-DOX. This knowledge is paramount to improve the efficiency of pH-sensitive liposomes or to be used as a rational strategy for developing new formulations to be applied in vivo.Item Physical and biological effects of paclitaxel encapsulation on disteraroylphosphatidylethanolamine-polyethyleneglycol polymeric micelles.(2020) Oda, Caroline Mari Ramos; Gasperini, Antonio Augusto Malfatti; Souza, Angelo Malachias de; Lana, Gwenaelle Elza Nathalie Pound; Mosqueira, Vanessa Carla Furtado; Fernandes, Renata Salgado; Oliveira, Mônica Cristina de; Barros, André Luís Branco de; Leite, Elaine AmaralSimple size observations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000) polymeric micelles (PM) with different compositions including or not paclitaxel (PTX) are unable to evidence changes on the nanocarrier structure. In such system a detailed characterization using highly sensitive techniques such as X-ray scattering and asymmetric flow field flow fractionation coupled to multi-angle laser light scattering and dynamic light scattering (AF4-MALS-DLS) is mandatory to observe effects that take place by the addition of PTX and/or more lipid-polymer at PM, leading to complex changes on the structure of micelles, as well as in their supramolecular organization. SAXS and AF4-MALS-DLS suggested that PM can be found in the medium separately and highly organized, forming clusters of PM in the latter case. SAXS fitted parameters showed that adding the drug does not change the average PM size since the increase in core radius is compensated by the decrease in shell radius. SAXS observations indicate that PEG conformation takes place, changing from brush to mushroom depending on the PM composition. These findings directly reflect in in vivo studies of blood clearance that showed a longer circulation time of blank PM when compared to PM containing PTX.Item Paclitaxel-loaded pH-sensitive liposome : new insights on structural and physicochemical characterization.(2018) Monteiro, Liziane Oliveira Fonseca; Souza, Angelo Malachias de; Lana, Gwenaelle Elza Nathalie Pound; Paniago, Rogerio Magalhães; Mosqueira, Vanessa Carla Furtado; Oliveira, Mônica Cristina de; Barros, André Luís Branco de; Leite, Elaine AmaralA long-circulating and pH-sensitive liposome containing paclitaxel (SpHL-PTX) was recently developed by our group. Once in an acidic environment, for example, tumors, these liposomes undergo destabilization, releasing the encapsulated drug. In this way, the aim of this study was to evaluate the molecular and supramolecular interactions between the lipid bilayer and PTX in similar biological environment conditions. High-sensitivity analyses of SpHL-PTX structures were obtained by the small-angle X-ray scattering technique combined with other techniques such as dynamic light scattering, asymmetric flow field-flow fractionation, transmission electron microscopy, and high-performance liquid chromatography. The results showed that PTX incorporation in the liposomal bilayer clearly leads to changes in supramolecular organization of dioleoylphosphatidylethanolamine (DOPE) molecules, inducing the formation of more ordered structures. Changes in supramolecular organization were observed at lower pH, indicating that pH sensitivity was preserved even in the presence of fetal bovine serum proteins. Furthermore, morphological and physicochemical characterization of SpHL-PTX evidenced the formation of nanosized dispersion suitable for intravenous administration. In conclusion, a stable nanosized dispersion of PTX was obtained at pH 7.4 with suitable parameters for intravenous administration. At lower pH conditions, the pH sensitivity of the system was clearly evidenced by changes in the supramolecular organization of DOPE molecules, which is crucial for the delivery of PTX into the cytoplasm of the targeted cells. In this way, the results obtained by different techniques confirm the feasibility of SpHL as a promising tool to PTX delivery in acidic environments, such as tumors.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.