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Biomedical subjects

Gustavo A Abraham

Publications and source records attributed to Gustavo A Abraham.

8 recordsLinked to original sources

Controlled release of 5-fluorouridine from radiation-crosslinked poly(ethylene-co-vinyl acetate) films.

The effect of gamma-radiation doses of 12.5-380 kGy on the infrared spectra, gel content, mechanical properties, and the release of oxobutyl-5-fluoro-2'-deoxyuridine (OfdUrd, an antitumor agent) from poly(ethylene-co-vinyl acetate) (EVA) films was studied. The results showed that the application of radiation doses produced a crosslinking reaction leading to a maximum gel content of about 85% in the case of 150 kGy. Higher doses did not increase the gel content in EVA films. The mechanical properties (tensile strength, percentage elongation at break and Young's modulus) of all studied EVA matrices were affected by the exposure to gamma-radiation. Irradiation doses over 50 kGy caused an increase in the Young's modulus of EVA and at the same time a decrease in the strain per cent. Moreover, the network structure formed after irradiation reduced significantly the OFdUrd release from EVA films. In this manner, the radiation dose applied to the polymeric matrix modulated the release of OFdUrd, avoiding the high concentrations that may cause severe systemic toxicity. The loading of OFdUrd to EVA film triggered a slight hyperemia after implantation, while the inflammatory reaction was only observed during the first two days.

Animals↗

Bioresorbable poly(ester-ether urethane)s from L-lysine diisocyanate and triblock copolymers with different hydrophilic character.

Bioresorbable linear poly(ester-ether urethane)s with different hydrophilic character were synthesized from block copolymers of poly(epsilon-caprolactone)-poly(ethylene oxide)-poly(epsilon-caprolactone) (PCL-PEO-PCL) as macrodiols, and L-lysine diisocyanate (LDI). A series of PCL-PEO-PCL triblock copolymers with different PEO and PCL chain length was obtained by reacting PEO with epsilon-caprolactone. Polyurethanes were synthesized by reacting the triblock copolymers with LDI in solution using stannous 2-ethylhexanoate as catalyst. The prepared triblock copolymers and polyurethanes were fully characterized by proton nuclear magnetic resonance spectroscopy, size exclusion chromatography, differential scanning calorimetry, and wide-angle X-ray diffraction. Water uptake, hydrolytic stability, and tensile properties of polyurethanes with different composition were evaluated and discussed in terms of the chain length and molecular weight of the polymers and its block components. Water uptake seems to depend on the ethylene oxide unit content of the polyurethane regardless of the triblock structure. Mechanical properties of the synthesized polymers were strongly affected by the molecular weight achieved during polymerization. The use of triblock macrodiols with different hydrophilicity allowed the preparation of a series of polyurethanes having a broad range of properties.

Biocompatible Materials↗

Antithrombogenic properties of bioconjugate streptokinase-polyglycerol dendrimers.

Dendrimers are monodisperse, spherical and hyperbranched synthetic macromolecules with a large number of surface groups that have the potential to act as carriers for drug immobilization by covalent binding or charge transfer complexation. In this work, a bioconjugate of streptokinase and a polyglycerol dendrimer (PGLD) generation 5 was used to obtain fibrinolytic surfaces. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography (GPC), nuclear magnetic resonance (1H-NMR, 13C-NMR) and matrix assisted laser desorption/ionization (MALDI-TOF) techniques. The synthesized dendrimer presented low dispersion in molecular weights (Mw/Mn = 1.05) and a degree of branching of 0.82 which characterize the polymer dendritic structure. The blood compatibility of the bioconjugate PGLD-Sk was evaluated by in vitro assays such as platelet adhesion and thrombus formation. Uncoated polystyrene -microtitre plates (ELISA) was used as reference. The epifluorescence microscopy results indicate that PGLD-Sk coating showed an improved antithrombogenic character relative to the uncoated ELISA plates.

Biocompatible Materials↗

Central neural tumor destruction by controlled release of a synthetic glycoside dispersed in a biodegradable polymeric matrix.

An octyl N-acetylglucosaminide derivative with a pentaerythritol chain at position 6 has been synthesized and evaluated as an inhibitor of neural tumor growth. The glycoside inhibited the growth of a neuroectodermic tumor implanted in rats and, when loaded on a slow-delivery polymer disk, caused the destruction of cultured human astroblastoma obtained after surgical biopsy.

Acetylglucosamine↗

Polymeric matrices based on graft copolymers of PCL onto acrylic backbones for releasing antitumoral drugs.

Graft copolymers of poly(epsilon-caprolactone) (PCL) on poly(dimethylacrylamide) (PDMAm), poly(methylmethacrylate) (PMMA), or on copolymers of poly(DMAm-co-MMA) have been synthesized and characterized by (1)H NMR spectroscopy, differential scanning calorimetry (DSC), and size exclusion chromatography (SEC). These partially biodegradable copolymer matrices have been proposed as drug delivery systems for the release of low-molecular-weight glycosides. Octyl-N-acetyl-6-O-[2,2-bis(hydroxymethyl)-3-hydroxypropyl]-alpha-D-glucosamide, a synthetic carbohydrate able to inhibit the proliferation of human malignant glioma cells in culture and transplanted glioma in rats was selected as drug model. The in vitro aqueous behavior of four drug-loaded and unloaded graft copolymers of different MMA: DMAm and PCL ratios has been analyzed performing swelling, degradation, and drug release experiments. An intimate dependence of the aqueous behavior with the composition has been found. The higher was the DMAm content, the higher was the hydrophilicity of the synthesized systems as well as the swelling, degradation, and drug release rate. In vivo experiments in pigs demonstrated the very good tolerance of drug-loaded implanted polymeric discs, and that >95% of the charged drug is released after 2 months' implantation.

Acrylamides↗

Crosslinkable PEO-PPO-PEO-based reverse thermo-responsive gels as potentially injectable materials.

This paper describes the functionalization and crosslinking of PluronicRTM derivatives in aqueous solution at 37 degrees C. Pluronic dimethacrylate was obtained by reacting native PEO-PPO-PEO triblocks with methacryloyl chloride and then crosslinking them by free radical polymerization at 37 degrees C, using a redox system. The resulting gel and its rheological behavior were characterized by different techniques. The swelling study of the crosslinked polymer was indicative of its reverse thermo-responsive behavior, as illustrated by the almost 800% water uptake of the polymer at 37 degrees C, as opposed to the 1600% attained by the polymer at 25 degrees C. As expected, while the Pluronic dimethacrylate gel displayed an Ec value of 142.5 +/- 29.7 kPa at 37 degrees C, the crosslinked system attained a Young's modulus three times higher: 415.2 +/- 45.7 kPa. Finally, the environmental SEM analysis revealed the porous microstructure of the crosslinked gels.

Biocompatible Materials↗

Self-curing acrylic formulations containing PMMA/PCL composites: properties and antibiotic release behavior.

Partially biodegradable acrylic composites containing poly(methyl methacrylate)-poly(epsilon-caprolactone) (PMMA/PCL) systems were prepared by mixing the corresponding PMMA/PCL beads (89:11, 86:14, 83:17, and 77:23 weight ratio) used as solid phase with methyl methacrylate (MMA) (liquid phase) in a solid/liquid ratio of 1.5:1. The physical and chemical microheterogeneity of these beads influenced significantly the curing parameters, because several aspects involved in the polymerization reaction are closely related to both morphology and size distribution of the particles. In vitro behavior was studied by immersion in simulated body fluid at pH = 7.4 and 37 degrees C for more than 8 weeks and the composition was followed by 1H-nuclear magnetic resonance spectroscopy. Approximately 2% wt/wt weight loss was observed after a period of 8 weeks for the composites richest in PCL. Mechanical properties of the dry and wet specimens were evaluated by compressive and tensile tests. In all cases, the presence of PCL in the composites provided a significant decrease in both compressive strength and elastic modulus compared with plain PMMA. Tensile and compressive strength also decreased significantly after 2 weeks of immersion in simulated body fluid compared with dry specimens. The self-curing composites based on PMMA/PCL beads and loaded with 3% wt/wt vancomycin were evaluated as carriers for local release of antibiotics. The composite prepared with beads of PMMA/PCL ratio 86:14 was the most effective. It eluted 64% of the initial drug within the first 5 h, allowing progressive release of nearly the total amount of the initial drug (90%) in approximately 2 months. The results obtained suggest that the described composites can be suitable for antibiotic release in non-load bearing graft applications.

Biocompatible Materials↗

Immobilization of a nonsteroidal antiinflammatory drug onto commercial segmented polyurethane surface to improve haemocompatibility properties.

A method has been developed in which a layer of p-aminosalicylic acid (4-amino-2-hydroxybenzoic acid) (PAS), a water soluble pharmaceutical compound of the nonsteroidal anti-inflammatory drug (NSAID) class with antiaggregant platelet activity, is covalently immobilized onto a segmented polyurethane, Biospan (SPU) surface. Thus, SPU surfaces were modified by grafting of hexamethylenediisocyanate. and the free isocyanate remaining on the SPU surface were then coupled through a condensation reaction to amine groups of p-aminosalicylic acid. The bonding of PAS from aqueous solution onto SPU surface was studied by ATR-FTIR. UV and fluorescence spectroscopy. Plateau levels of coupled PAS were reached within 1.2 microg/cm2 using PAS solution concentrations of 1mg/ ml. The surface wettability of the polymeric films measured by contact angle indicate that the introduction of the PAS turns the surface more hydrophilic (theta(water) = 43.1 +/- 2.1) relatively to the original SPU films (theta(water) = 70.3 +/- 1.9). The in vitro albumin (BSA) adsorption shows that the PAS-SPU films adsorb more BSA (250/microgmm2) than the original SPU (112 microg mm2). Thrombogenicity was assessed by measuring the thrombus formation and platelet adhesion of the SPU containing PAS relatively to nonmodified SPU surfaces. The polymeric surfaces with immobilized PAS had better nonthrombogenic characteristics as indicated by the low platelet adhesion, high adsorption of albumin relatively to fibrinogen and low thrombus formation, making them potentially good candidates for biomedical applications.

Albumins↗