Comunidades no DSpace

Selecione uma comunidade para navegar por suas coleções

Agora exibindo 1 - 3 de 3

Submissões Recentes

Item
Winged-cone conformation in hexa-p-tert-butylcalix[6]arene driven by the unusually strong guest encapsulation
(2017-08-31) Martins, Felipe Terra; Oliveira, Breno Germano de Freitas; Sarotti, Ariel Marcelo; Fátima, Ângelo de
Hexa-p-tert-butylcalix[6]arene (1) is believed to adopt a winged conformation in a solution, featured by four phenyl rings perpendicular to the calix basis and two others at 1,4-positions lying down. However, there is some controversy on the occurrence of this conformation because it has never been found in the solid state of calix[6]arenes, regardless of the substitution pattern at lower and upper rims. Here, we have observed the winged-cone conformation for the first time in a solvate form of 1 with dimethyl sulfoxide (DMSO), dimethylformamide, and pyridine. The DMSO molecule is strongly encapsulated into 1 through two OH···O hydrogen bonds with both flattened phenolic moieties, one lp(S)···π and four CH···π interactions with the four perpendicular phenyl rings. This host–guest complex has energy lower by 23.4 kcal mol–1 than the isolated species. In addition, another DMSO solvate form with 1,2,3-alternate conformation was also obtained in this study, and its structure is compared with that of the precedent one. A detailed density functional theory study has also been carried out to understand the energetic relationships among cone conformers, intramolecular hydrogen-bonding patterns, and DMSO encapsulation.
Item
Preparation of a solid self-microemulsifying drug delivery system by hot-melt extrusion
(2018) Silva, Luís Antônio Dantas; Almeida, Susana Leão; Pineze, Ellen Cristine; Gonçalves, Priscila Bianca Rodrigues da Rocha; Martins, Felipe Terra; Freitas, Luis Alexandre Pedro de; Taveira, Stephânia Fleury; Cunha Filho, Marcilio Sérgio Soares da; Marreto, Ricardo Neves
Hot-melt extrusion (HME) has gained increasing attention in the pharmaceutical industry; however, its potential in the preparation of solid self-emulsifying drug delivery systems (S-SMEDDS) is still unexplored. This study sought to prepare enteric S-SMEDDS by HME and evaluate the effects of the process and formulation variables on S-SMEDDS properties via Box-Behnken design. Liquid SMEDDS were developed, and carvedilol was used as a class II model drug. Mean size, polydispersity index (PdI) and zeta potential of the resulting microemulsions were determined. The extrudates were then obtained by blending the lipid mixture and HPMCAS using a twin-screw hot-melt extruder. SEM, optical microscopy and PXRD were used to characterize the extrudates. In vitro microemulsion reconstitution and drug release were also studied. L-SMEDDS gave rise to microemulsions with low mean size, PdI and zeta potential (140.04 ± 7.22 nm, 0.219 ± 0.011 and −9.77 ± 0.86 mV). S-SMEDDS were successfully prepared by HME, and an HMPCAS matrix was able to avoid microemulsion reconstitution and retain drug release in pH 1.2 (12.97%–25.54%). Conversely, microemulsion reconstitution and drug release were gradual in pH 6.8 and complete for some formulations. Extrudates prepared at the lowest drug concentration and highest temperature and recirculation time promoted a complete and rapid drug release in pH 6.8 giving rise to small and uniform microemulsion droplets.
Item
[Ru(pipe)(dppb)(bipy)]PF6: a novel ruthenium complex that effectively inhibits ERK activation and cyclin D1 expression in A549 cells
(2017-08-01) Silva, Guilherme Álvaro Ferreira da; Ortega, Marina Montingelli; Banionis, Marco Aurélio; Garavelli, Graciana Yokota; Martins, Felipe Terra; Dias, Júlia Scaff Moreira; Viegas Junior, Claudio; Oliveira, Jaqueline Carvalho de; Nascimento, Fábio Batista do; Doriguetto, Antonio Carlos; Barbosa, Marília Imaculada Frazão; Ionta, Marisa
Lung cancer is the most frequent type of cancer worldwide. In Brazil, only 14% of the patients diagnosed with lung cancer survived 5 years in the last decades. Although improvements in the therapeutic approach, it is relevant to identify new chemotherapeutic agents. In this framework, ruthenium metal compounds emerge as a promising alternative to platinum-based compounds once they displayed lower cytotoxicity and more selectivity for tumor cells. The present study aimed to evaluate the antitumor potential of innovative ruthenium(II) complex, [Ru(pipe)(dppb)(bipy)]PF6 (PIPE) on A549 cells, which is derived from non-small cell lung cancer. Results demonstrated that PIPE effectively reduced the viability and proliferation rate of A549 cells. When PIPE was used at 9 μM there was increase in G0/G1 cell population with concomitant reduction in frequency of cells in S-phase, indicating cell cycle arrest in G1/S transition. Antiproliferative activity of PIPE was associated to its ability of reducing cyclin D1 expression and ERK phosphorylation levels. Cytotoxic activity of PIPE on A549 cells was observed when PIPE was used at 18 μM, which was associated to its ability of inducing apoptosis by intrinsic pathway. Taken together, the data demonstrated that PIPE is a promising antitumor agent and further in vivo studies should be performed.
Item
Spatio-temporal image correlation analysis for 3D flow field mapping in microfluidic devices
(2017) Ceffa, Nicolò Giovanni; Bouzin, Margaux; D'Alfonso, Laura; Sironi, Laura; Marquezin, Cassia Alessandra; Auricchio, Ferdinando; Marconi, Stefania; Chirico, Giuseppe; Collini, Maddalena
Microfluidic devices reproducing 3D networksare particularly valuable for nanomedicine applications such astissue engineering and active cell sorting. There is however agap in the possibility to measure how theflow evolves in such3D structures. We show here that it is possible to map 3Dflows in complex microchannel networks by combining widefield illumination to image correlation approaches. For thispurpose, we have derived the spatiotemporal image correlationanalysis of time stacks of single-plane illumination microscopyimages. From the detailed analytical and numerical analysis ofthe resulting model, we developed afitting method that allowsus to measure, besides the in-plane velocity, the out-of-plane velocity component down tovz≅65μm/s. We have applied thismethod successfully to the 3D reconstruction offlows in microchannel networks with planar and 3D ramifications. Thesedifferent network architectures have been realized by exploiting the great prototyping ability of a 3D printer, whose precision canreach few tens of micrometers, coupled to poly dimethyl-siloxane soft-printing lithography.
Item
Molecular collisions or resonance energy transfer in lipid vesicles? A methodology to tackle this question
(2021) Marquezin, Cassia Alessandra; Lamy, Maria Teresa Moura; Souza, Eduardo Sérgio de
In this work, molecular interactions in a lipid membrane are discussed through fluorescence spectroscopy data, both experimentally and theoretically. In particular, the fluorescence quenching mechanisms between the fluorescent probe 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan) and the potential drug 2-nitrobenzaldehyde-thiosemicarbazone (2-TSC) were studied, both inserted in a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DMPC) model membrane. The fluorescence intensity and the lifetime of Laurdan decrease dramatically in the presence of 2-TSC, in both gel and fluid phases of the DMPC bilayer. It is shown here how to identify the correct quenching mechanism, by conducting a careful analysis of the fluorescence data. The analysis of the bimolecular constant values obtained through the Stern-Volmer equation, considering the collisional mechanism, made clear the incompatibility of the obtained values with estimated diffusion coefficients for Laurdan and 2-TSC inserted into lipid bilayers. On the other hand, using the Förster’s theory of resonance energy transfer (FRET) we obtained results in good agreement with the already known dynamic characteristics of a DMPC bilayer, at its both gel and fluid phases. Through spectroscopy data and computational calculation, Förster distance, energy transfer efficiency and distance distribution were obtained for the donor/acceptor pair Laurdan/2-TSC, at both gel and fluid phases of the bilayer. The distance distribution reflects the occurrence of FRET involving donor/acceptor pairs in the same leaflet of the lipid bilayer and pairs in opposite leaflet, and these results are in good agreement with our previous proposal about the lateral organization and position of Laurdan and 2-TSC molecules in a DMPC bilayer. All these results lead us to conclude that FRET between the donor Laurdan and the acceptor 2-TSC is the mechanism responsible for non-radiative deexcitation of Laurdan. The methodology used here could be extended to other pairs of donor/acceptor molecules, to contribute to the knowledge about their localizations in lipid membranes.