DEFAR - Artigos publicados em periódicos
URI permanente para esta coleçãohttp://www.hml.repositorio.ufop.br/handle/123456789/531
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Item Interactions between a macrophage cell line (J774A1) and surface-modified poly(D, L-lactide) nanocapsules bearing poly(ethylene glycol).(1999) Mosqueira, Vanessa Carla Furtado; Legrand, Philippe; Gref, Ruxandra; Heurtault, Béatrice; Appel, M.; Barratt, GillianThe interactions of naked and surface-modified poly(D,L-lactic acid) (PLA) nanocapsules (NC), where polyethyleneglycol (PEG) was adsorbed or covalently attached, have been studied with a macrophage-like cell line. The fluorescent oil marker, DiD, was successfully encapsulated in NCs in order to follow their interactions with cells. The cell-associated fluorescence obtained with PEG-PLA NC was about 3- to 13-fold lower than that obtained with naked-PLA NC. The effects of PEG chain length, its content as a percentage of total polymer and NC concentration in the culture medium were evaluated. PEG-PLA NC showed dramatically reduced fluorescence association with cells during an 18 h incubation compared with naked-PLA NC, showing that covalent attachment of PEG is important for the persistence of low uptake. The best results in reducing cell-associated fluorescence were obtained with a surface-modified PEG-PLA NC bearing a chain with 20000 MW. Increasing the percentage of PEG produced a reduction in marker association for a given PEG chain length. Moreover, when the PEG-containing poloxamer was simply adsorbed, marker association was dependent on the extent of dilution and the type of serum in the culture medium. Serum proteins, especially immunoglobulins, increased cell-associated fluorescence for PEG-adsorbed NC, but had very little effect on PEG-PLA NC. Marker association was only partially inhibited in the presence of cytochalasin B. The mechanisms of cell-NC interaction depended on the characteristics of the NC surface in each formulation. When the NC was physically separated from cells no diffusion of fluorescent marker in aqueous medium occurred. Nevertheless, collision-mediated transfer of DiD from NC to J774 cells was a non-negligible route of marker transfer, mainly for naked NC. However, this collision-mediated transfer was reduced for the PEG-PLA NC probably due to the restricted contact between NC and cells afforded by PEG steric hindrance at the surface.Item PLA-PEG nanocapsules radiolabeled with 99mTechnetium-HMPAO : release properties and physicochemical characterization by atomic force microscopy and photon correlation spectroscopy.(2008) Pereira, Maira Alves; Mosqueira, Vanessa Carla Furtado; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Ramaldes, Gilson Andrade; Cardoso, Valbert NascimentoThe present work describes the preparation, characterization and labelling of conventional and surface-modified nanocapsules (NC) with 99mTc-HMPAO. The size, size distribution and homogeneity were determined by photon correlation spectroscopy (PCS) and zeta potential by laser doppler anemometry. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The stability and release profile of the NC were determined in vitro in plasma. The results showed that the use of methylene blue induces significant increase in the encapsulation efficiency of 99mTc-HMPAO, from 24.4 to 49.8% in PLANC and 22.37 to 52.93% in the case of PLA-PEGNC(P < 0.05) by improving the complex stabilization. The average diameter of NC calculated by PCS varied from 216 to 323 nm, while the average diameter determined by AFM varied from 238 to 426 nm. The AFM analysis of diameter/height ratios suggested a greater homogeneity of the surface-modified PLAPEG nanocapsules compared to PLA NC concerning their flattening properties. The in vitro release of the 99mTc-HMPAO in plasma medium was faster for the conventional PLA NC than for the surface-modified NC. For the latter, 60% of the radioactivity remained associated with NC, even after 12h of incubation. The results suggest that the surface-modified 99mTc-HMPAO-PLA PEG NCwas more stable against label leakage in the presence of proteins and could present better performance as radiotracer in vivo.Item Polymeric nanostructures for drug delivery : characterization by atomic force microscopy.(2005) Mosqueira, Vanessa Carla Furtado; Leite, Elaine Amaral; Barros, Cristina Maria de; Vilela, José Mário Carneiro; Andrade, Margareth SpanglerItem Release profiles and morphological characterization by atomic force microscopy and photon correlation spectroscopy of 99mTechnetium-fluconazole nanocapsules.(2008) Assis, Danielle Nogueira de; Mosqueira, Vanessa Carla Furtado; Vilela, José Mário Carneiro; Andrade, Margareth Spangler; Cardoso, Valbert NascimentoSeveral classes of antifungal have been employed in candidiasis treatment, but patients with advanced immunodeficiency can present unsatisfactory results after therapy. In these cases, high doses of drugs or the use of multiple agents are sometimes used, and hence increasing the risk of serious side effects. Considering theses difficulties, the encapsulation of antifungal agents in nanoparticulate carriers has been used with the objective of modifying the pharmacokinetic of drugs resulting in more efficient treatments with less side effects. The purpose of this work was the preparation, characterization and the investigation of the release profiles of radiolabeled fluconazole nanocapsules. The size, homogeneity and zeta potential of NC preparations were determined with a Zetasizer 3000HS. The morphology and the structural organization were evaluated by atomic force microscopy (AFM). The release study in vitro of NC was evaluated in physiologic solution with or without 70% mouse plasma. The labeling yield of fluconazole with 99mTc was 94% and the radiolabeled drug was stable within 24 h period. The encapsulation percentage of 99mTc-fluconazole in PLA-POLOX NC and PLA-PEG NC was approximately of 30%. The average diameter calculated by photon correlation spectroscopy (PCS) varied from 236 to 356 nm, while the average diameter determined by AFM varied from 238 to 411 nm. The diameter/height relation decreased significantly when 25% glutaraldehyde was used for NC fixation on mica. The zeta potential varied from −55 to −69 nm and surface-modified NC showed lower absolute values than conventional NC. The in vitro release of 99mTc-fluconazole in plasma medium of the conventional and surface-modified NC was greater than in saline. The drug release in plasma medium from conventional NC was faster than for surface-modified NC. The results obtained in this work suggest that the nanocapsules containing fluconazole could be used to identify infectious foci, due to the properties, such as size, zeta potential and controlled release of 99mTc-fluconazole. The surface-modified nanocapsules could constitute a long-circulating intravenous formulation of fluconazole for treating sepsis caused by disseminated form of candidiasis. However, in vivo studies should be considered and are under investigation.Item Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modifed nanocapsules.(2001) Mosqueira, Vanessa Carla Furtado; Legrand, Philippe; Gulik, Annette; Bourdon, Olivier; Gref, Ruxandra; Labarre, Denis; Barratt, GillianThe aim of our work was to examine the relationship between modi"cations of the surface of nanocapsules (NC) by adsorption or covalent grafting of poly(ethylene oxide) (PEG), and changes in their phospholipid (PL) content on complement activation (C3 cleavage) and on uptake by macrophages. The physicochemical characterization of the NC included an investigation of their properties, such as surface charge, size, hydrophilicity, morphology and homogeneity. This is the "rst time that such properties have been correlated with biological interactions for NC, a novel carrier system with a structure more complex than nanospheres. C3 crossed immunoelectrophoresis revealed the reduced activation for NC with longer PEG chain and higher density, although all formulations induced C3 cleavage to a lesser or greater extent. NC bearing PEG covalently bound to the surface were weaker activators of complement than plain PLA [poly(D,L-lactide)] NC or nanospheres (NS). Furthermore, the #uorescent/confocal microscopy of J774A1 cells in contact with NC reveal a dramatically reduced interaction with PEG-bearing NC. However, the way in which PEG was attached (covalent or adsorbed) seemed to a!ect the mechanism of uptake. Taken together, these results suggest that the low level of protein binding to NC covered with a high density of 20 kDa PEG chains is likely to be due to the steric barriers surrounding these particles, which prevents protein adsorption and reduces their interaction with macrophages. 2001 Elsevier Science Ltd. All rights reserved.Item Poly-caprolactone nanocapsules morphological features by atomic force microscopy.(2005) Leite, Elaine Amaral; Vilela, José Mário Carneiro; Mosqueira, Vanessa Carla Furtado; Andrade, Margareth SpanglerItem Cardiotoxicity reduction induced by halofantrine entrapped in nanocapsule devices.(2007) Leite, Elaine Amaral; Guimarães, Andrea Grabe; Guimarães, Homero Nogueira; Coelho, George Luiz Lins Machado; Barratt, Gillian; Mosqueira, Vanessa Carla FurtadoThe main objective of the present study was to evaluate the reduction in halofantrine (Hf) toxicity, an antimalarial drug frequently associated with QT interval prolongation in electrocardiogram, by its entrapment in poly-ε-caprolactone nanocapsules (NC). The acute lethal dose (LD100) of Hf.HCl experimentally observed was 200 mg/kg whereas the calculated LD50 was 154 mg/kg. In contrast, the LD100 for Hf-NC was 300 mg/ kg with a longer mean time to death than Hf.HCl. The calculated LD50 was 249 mg/kg for Hf-NC. The Hf entrapped in PCL NC presented a greater efficacy than PLA-PEG NC and than Hf solution in P. berghei-infected mice at 1 mg/kg. The cardiovascular parameters, ECG and arterial blood pressure, were evaluated in anaesthetized Wistar rats after the IV administration of a single, especially high dose (100 and 150 mg/kg) of halofantrine base loaded-nanocapsules (Hf-NC) or halofantrine chlorhydrate (Hf.HCl) solution. It was observed that Hf solution caused prolongation of the QT and PR intervals of the ECG; however, this effect was significantly (Pb0.001) reduced when Hf was administered entrapped in nanocapsules. The treatment with Hf.HCl induced a pronounced bradycardia and severe hypotension leading to death. The effect of Hf-NC upon heart rate was reduced from 58 to 75% for 100 and 150 mg/kg, respectively, when compared with Hf.HCl solution. These findings show that the encapsulation of halofantrine reduces the QT interval prolongation of ECG in rats and suggest that a modification of drug distribution was possible by using nanocapsules. Hf encapsulation was the main factor responsible for the significant reduction in cardiac toxicity observed.