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Publicaciones científicas más recientes (desde 2010)

Autores: Carbajo-Gordillo, A. I.; Rodriguez-Lavado, J.; Jiménez-Blanco, J. L.; et al.
Revista: CHEMICAL COMMUNICATIONS
ISSN 1359-7345  Vol. 55  2019  págs. 8227 - 8230
An original family of multivalent vectors encompassing gemini and facial amphiphilicity, namely cationic Siamese twin surfactants, has been prepared fromthe disaccharide trehalose; molecular engineering lets us modulate the self-assembling properties and the topology of the nanocomplexes with plasmid DNA for efficient gene delivery in vitro and in vivo.
Autores: Rochin-Wong, S.; Rosas-Durazo, A. ; Zavala-Rivera, P. ; et al.
Revista: POLYMERS
ISSN 2073-4360  Vol. 10  Nº 7  2018  págs. 760
Engineering of multifunctional drug nanocarriers combining stability and good release properties remains a great challenge. In this work, natural polymers kappa-carrageenan (kappa-CAR) and chitosan (CS) were deposited onto olive oil nanoemulsion droplets (NE) via layer-by-layer (LbL) self-assembly to study the release mechanisms of the anti-inflammatory diflunisal (DF) as a lipophilic drug model. The nano-systems were characterized by dynamic light scattering (DLS), zeta potential (zeta-potential) measurements, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy (XEDS) and Fourier transform infrared spectroscopy (FTIR) to confirm the NE-coating with polymer layers. In addition, kinetic release studies of DF were developed by the dialysis diffusion bag technique. Mathematical models were applied to investigate the release mechanisms. The results showed that stable and suitably sized nanocapsules (similar to 300 nm) were formed. Also, the consecutive adsorption of polyelectrolytes by charge reversal was evidenced. More interestingly, the drug release mechanism varied depending on the number of layers deposited. The nanosized systems containing up to two layers showed anomalous transport and first order kinetics. Formulations with three and four layers exhibited Case II transport releasing diflunisal with zero order kinetics.
Autores: Figueroa-Pizano, M. D.; Vélaz, I.; Peñas, Francisco Javier; et al.
Revista: CARBOHYDRATE POLYMERS
ISSN 0144-8617  Vol. 195  2018  págs. 476 - 485
The freezing-thawing is an advantageous method to produce hydrogels without crosslinking agents. In this study chitosan-poly(vinyl alcohol) (CS-PVA) hydrogels were prepared by varying the freezing conditions and composition, which affect the final characteristics of the products. The swelling degree, morphology, porosity, and diflunisal drug loading, as well as the drug release profiles were evaluated. The hydrogel swelling ratio was found to be mainly affected by the CS content, the number of freezing cycles and the temperature. SEM micrographs and porosity data confirm that pore size increases with the chitosan content. However, the use of either lower temperatures or longer freezing times, results in higher porosity and smaller pores. The drug release times of the CS-PVA hydrogels were as long as 30 h, and according to the mathematical fitting, a simple diffusion mechanism dominates the process. Moreover, a mathematical model predicting the hydrogels physical and structural behavior is proposed.
Autores: Gonzalez, E. A. S.; Olmos, D. , (Autor de correspondencia); Lorente, M. A. ; et al.
Revista: POLYMERS
ISSN 2073-4360  Vol. 10  Nº 12  2018  págs. 1365
Polymer composite materials based on polylactic acid (PLA) filled with titanium dioxide (TiO2) nanoparticles were prepared. The aim of this work was to investigate the antibacterial action of TiO2 against a strain of E. coli (DH5) to obtain information on their potential uses in food and agro-alimentary industry. PLA/TiO2 systems were prepared by a two-step process: Solvent casting followed by a hot-pressing step. Characterization was done as a function of particle size (21 nm and <100 nm) and particle content (0%, 1%, 5%, 10%, and 20%, wt %). Structural characterization carried out by X-ray diffraction (XRD) and Fourier Transformed Infrared spectroscopy (FTIR) did not reveal significant changes in polymer structure due to the presence of TiO2 nanoparticles. Thermal characterization indicated that thermal transitions, measured by differential scanning calorimetry (DSC), did not vary, irrespective of size or content, whereas thermogravimetric analysis (TGA) revealed a slight increase in the temperature of degradation with particle content. Bacterial growth and biofilm formation on the surface of the composites against DH5 Escherichia coli was studied. Results suggested that the presence of TiO2 nanoparticles decreases the amount of extracellular polymeric substance (EPS) and limits bacterial growth.
Autores: Gallego-Yerga, L.; Benito, J. M.; et al.
Revista: CHEMISTRY-A EUROPEAN JOURNAL
ISSN 0947-6539  Vol. 24  Nº 15  2018  págs. 3825 - 3835
Engineering self-assembled superstructures through complexation of plasmid DNA (pDNA) and single-isomer nanometric size macromolecules (molecular nanoparticles) is a promising strategy for gene delivery. Notably, the functionality and overall architecture of the vector can be precisely molded at the atomic level by chemical tailoring, thereby enabling unprecedented opportunities for structure/self-assembling/pDNA delivery relationship studies. Beyond this notion, by judiciously preorganizing the functional elements in cyclodextrin (CD)-based molecular nanoparticles through covalent dimerization, here we demonstrate that the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from spherical to ellipsoidal, rod-type, or worm-like nanoparticles, which makes it possible to gain understanding of their shape-dependent transfection properties. The experimental findings are in agreement with a shift from chelate to cross-linking interactions on going from primary-face- to secondary-face-linked CD dimers, the pDNA partner acting as an active payload and as a template. Most interestingly, the transfection efficiency in different cells was shown to be differently impacted by modifications of the CDplex morphology, which has led to the identification of an optimal prototype for tissue-selective DNA delivery to the spleen in vivo.
Autores: González-Gaitano, Gustavo; Isasi, José Ramón; Vélaz, I.; et al.
Revista: CURRENT PHARMACEUTICAL DESIGN
ISSN 1381-6128  Vol. 23  Nº 3  2017  págs. 411 - 432
The pharmaceutical applications of cyclodextrins (CDs), cyclic oligosaccharides capable of including hydrophobic molecules inside their cavities, have been known for decades. Besides the solubilising and encapsulating abilities of natural and modified CDs due to the formation of inclusion complexes, there is an increasing interest in organized macrostructures based on CDs as potential drug delivery devices and gene carrier systems. The present review discusses first the case of drug carriers based on monomeric modified CDs (amphiphilic and CD core-star polymers), in which self-assembly plays a major role. Polyrotaxanes, i.e., CDs threaded onto a polymer chain, are then reviewed in relation to their pharmaceutical applications. Finally, covalently linked CDs, either by grafting or crosslinking, are analyzed, including more complex structures formed by assembling CD-containing networks or chains. We have tried along this review to cover the most recent developments on these structures for drug delivery in a "beyond the cyclodextrin" approach. The review will be helpful, both for readers who want to be introduced into the world of these remarkable structures, or for specialists who are doing research in this field.
Autores: Vélaz, I.; Isasi, José Ramón, (Autor de correspondencia)
Revista: JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY
ISSN 1388-3127  Vol. 86  Nº 3 - 4   2016  págs. 283 - 289
Cyclodextrin (CD) hydrogels were synthesized by a crosslinking reaction with the same cyclodextrin/epichlorohydrin mole ratio (1/11) using alphaCD, ßCD, gammaCD, and 50:50 mixtures of alpha/ßCD and ß/gammaCD. In order to investigate the sorption capacity of these hydrogels to different solutes, five model molecules have been selected: phenol, 3-nitrophenol, 4-nitrophenol, 1-naphthol, and the antiinflamatory drug diflunisal. The amounts sorbed have been related to the different affinities of the solutes. 1-naphthol shows the highest affinity for these polymers, especially in the case of sorbents containing ßCD. The sorption is considerably poorer for phenol than for its nitro derivatives. The two structural isomers 3- and 4-nitrophenol show significant differences in their affinities towards alphaCD, ßCD and alpha/ßCD. Finally, in the case of diflunisal, a bulkier model molecule, remarkable differences were found on the sorption behaviour by polymers whose cyclodextrins have a similar affinity for this solute (ßCD, gammaCD, and ß/gammaCD).
Autores: Martínez-Oharriz, M.C.; Vélaz, I.; et al.
Revista: JOURNAL OF PHARMACEUTICAL SCIENCES
ISSN 0022-3549  Vol. 103  Nº 1  2014  págs. 197 - 206
Gels obtained by complexation of octablock star polyethylene oxide/polypropylene oxide copolymers ( Tetronic 90 R4) with alpha-cyclodextrin (alpha- CD) were evaluated as matrices for drug release. Both molecules are biocompatible so they can be potentially applied to drug delivery systems. Two different types of matrices of Tetronic 90 R4 and alpha-CD were evaluated: gels and tablets. These gels are capable to gelifying in situ and show sustained erosion kinetics in aqueous media. Tablets were prepared by freeze-drying and comprising the gels. Using these two different matrices, the release of two model molecules, L-tryptophan ( Trp), and a protein, bovine serum albumin ( BSA), was evaluated. The release profiles of these molecules from gels and tablets prove that they are suitable for sustained delivery. Mathematical models were applied to the release curves from tablets to elucidate the drug delivery mechanism. Good correlations were found for the fittings of the release curves to different equations. The results point that the release of Trp from different tablets is always governed by Fickian diffusion, whereas the release of BSA is governed by a combination of diffusion and tablet erosion.
Autores: Estévez, C. A.; Isasi, José Ramón; et al.
Revista: BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
ISSN 1860-5397  Vol. 10  2014  págs.  3127 - 3135
All mammals lose their ability to produce lactase (ß-galactosidase), the enzyme that cleaves lactose into galactose and glucose, after weaning. The prevalence of lactase deficiency (LD) spans from 2 to 15% among northern Europeans, to nearly 100% among Asians. Following lactose consumption, people with LD often experience gastrointestinal symptoms such as abdominal pain, bowel distension, cramps and flatulence, or even systemic problems such as headache, loss of concentration and muscle pain. These symptoms vary depending on the amount of lactose ingested, type of food and degree of intolerance. Although those affected can avoid the uptake of dairy products, in doing so, they lose a readily available source of calcium and protein. In this work, gels obtained by complexation of Tetronic 90R4 with ¿-cyclodextrin loaded with ß-galactosidase are proposed as a way to administer the enzyme immediately before or with the lactose-containing meal. Both molecules are biocompatible, can form gels in situ, and show sustained erosion kinetics in aqueous media. The complex was characterized by FTIR that evidenced an inclusion complex between the polyethylene oxide block and ¿-cyclodextrin. The release profiles of ß-galactosidase from two different matrices (gels and tablets) of the in situ hydrogels have been obtained. The influence of the percentage of Tetronic in media of different pH was evaluated. No differences were observed regarding the release rate from the gel matrices at pH 6 (t50 = 105 min). However, in the case of the tablets, the kinetics were faster and they released a greater amount of 90R4 (25%, t50 = 40¿50 min). Also, the amount of enzyme released was higher for mixtures with 25% Tetronic. Using suitable mathematical models, the corresponding kinetic parameters have been calculated. In all cases, the release data fit quite well to the Peppas¿Sahlin model equation, indicating that the release of ß-galactosidase is governed by a combination of diffusion and erosion processes. It has been observed that the diffusion mechanism prevails over erosion during the first 50 minutes, followed by continued release of the enzyme due to the disintegration of the matrix.
Autores: García-Padial, Marcos; Martínez-Oharriz, M.C.; Isasi, José Ramón; et al.
Revista: JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY
ISSN 1388-3127  Vol. 75  Nº 3-4  2013  págs. 241 - 246
Tyrosol (TY), 4-(2-hydroxyethyl)phenol, is an olive oil biophenol with antioxidant activity and positive effects on human health. This study has investigated the interactions of TY with cyclodextrins (CD) and a CD polymer. Complexation of TY with beta-CD, hydroxypropyl-beta-CD (HP-beta-CD), and methyl-beta-CD (Me-beta-CD) has been evaluated both in aqueous solution and in the solid state. The techniques employed in solution to determine the apparent stability constants of the respective complexes were fluorescence and UV-visible spectroscopies. Complexation with beta-CD and its derivatives involved an increase of both the UV absorbance and the intrinsic fluorescence of TY; a bathochromic shift of the UV spectrum was detected as well. The apparent stability constants obtained with native beta-CD, Me-beta-CD and HP-beta-CD presented similar values. Complexes in the solid state were obtained by coevaporation and kneading. They were characterised by X-ray diffraction analysis and differential thermal analysis. The interaction of TY with beta-CD led to a crystalline complex; the same diffraction pattern was obtained by coevaporation and kneading. The complexes obtained with methyl- and HP-beta-CD were amorphous irrespective of the preparation method. In addition, the retention of TY in an insoluble polymer of CD crosslinked with epichlorohydrin has been quantified. In approximately 20 min, 1 mg of TY per gram of polymer was retained.
Autores: Isasi, José Ramón; Vélaz, I.;
Revista: EUROPEAN POLYMER JOURNAL
ISSN 0014-3057  Vol. 49  Nº 12  2013  págs. 3912 - 3920
Hydrogel networks of ¿, ß or ¿-cyclodextrin (CD) and mixtures of ¿/ß or ß/¿ CDs have been obtained using epichlorohydrin (EP) as a crosslinking agent. Discs of the resulting polymers were evaluated as drug carriers for controlled release using the antiinflammatory naproxen (NAP) as a model drug. ßCD polymer (ßCDP) has shown the highest amount of drug loaded and the lowest one corresponds to the polymer containing ¿CD, in agreement with the affinities of NAP for the corresponding cyclodextrins. In addition, in vitro drug release kinetics assays from the loaded discs have been carried out. The different release profiles at simulated physiological conditions of pH and temperature have been correctly defined, identifying in each case the release mechanisms. Using suitable mathematical models, the apparent diffusional coefficients and the corresponding kinetic parameters have been calculated. It can be inferred that a simple Fickian diffusion mechanism occurs, except for the mixed polymers at pH 1.2 (anomalous transport) and in the case ¿CDP at pH 7.0 (burst phenomenon). Furthermore, the diffusion and relaxation contributions have been determined for the mixed polymers in order to achieve progress in the design of new polymer matrices according to the structure of the selected drugs.
Autores: Isasi, José Ramón; Vélaz, I.;
Revista: Carbohydrate Polymers
ISSN 0144-8617  Vol. 87  Nº 3  2012  págs. 2024 - 2030
Autores: Zornoza, Arantza; Isasi, José Ramón; et al.
Revista: Journal of Inclusion Phenomena and Macrocyclic Chemistry
ISSN 1388-3127  Vol. 69  Nº 3-4  2011  págs. 469 - 474
Autores: Fernández, L.; Zornoza, Arantza; et al.
Revista: Journal of Inclusion Phenomena and Macrocyclic Chemistry
ISSN 1388-3127  Vol. 69  Nº 3-4  2011  págs. 411 - 415
Autores: Maddens, T.; Vélaz, I.; et al.
Revista: Journal of Inclusion Phenomena and Macrocyclic Chemistry
ISSN 1388-3127  Vol. 70  Nº 3-4  2011  págs. 415 - 419
Autores: Zornoza, Arantza; et al.
Revista: Journal of Inclusion Phenomena and Macrocyclic Chemistry
ISSN 1388-3127  Vol. 66  Nº 3-4  2010  págs. 393 - 402
Terbinafine (TB) is an allylamine derivative used as oral and topical antifungal agent. The physicochemical properties of the complexes between TB and different cyclodextrins (CDs): alpha-CD, beta-CD, hydroxypropyl beta-CD, methyl beta-CD and gamma-CD, have been studied in pH 12 aqueous solutions at 25 A degrees C and in the solid state. Different phase solubility profiles of TB in the presence of CDs have been obtained: A(L) type for TB with hydroxypropyl beta-CD and gamma-CD, A(P) type for the complexes with methyl beta-CD and alpha-CD, while a B(S) profile was found for TB-beta-CD. The apparent stability constants of the complexes were calculated at 25 A degrees C from the phase solubility diagrams. The higher increase of TB solubility, up to 200-fold, together with the higher value of the stability constant were found for the complex with methyl beta-CD. Solid systems of 1:1 drug:CD molar ratio were prepared and characterised using X-ray diffraction patterns, thermal analysis and FTIR spectroscopy. The coevaporation method can be considered the best method in preparing these solid complexes. The complexes of TB with natural CDs, except with alpha-CD, were crystalline, whereas the methyl and hydroxypropyl derivatives gave rise to amorphous phases. Dissolution rate studies have been performed with TB-beta-CD and TB-HP beta-CD complexes, showing a positive influence of complexation on the drug dissolution.

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