Nuestros investigadores

Arantza Zornoza Cebeiro

Líneas de investigación
Complejos de inclusión con ciclodextrinas. Polímeros de ciclodextrina. Polimorfismo. Liberación controlada de fármacos. Encapsulación de antioxidantes.
Índice H
12, (Scopus, 29/06/2020)

Publicaciones científicas más recientes (desde 2010)

Autores: Zornoza Cebeiro, Arantza; Moreno, L. ; Puig Rigall, Joan; et al.
ISSN 0167-7322  Vol. 282  2019  págs. 205 - 212
The solubilisation of methylparaben (MP), an antimicrobial agent used as a food preservative and in cosmetics and personal-care products, in two poloxamines of different Hydrophilic-Lipophilic Balance (HLB), namely Tetronic 904 (T904) and 1107 (T1107), has been studied. The influence of the preservative on the aggregation behaviour of both Tetronics has been analysed by dynamic light scattering (DLS) and small-angle neutron scattering (SANS), while the precise location of the molecule in the aggregates as well as the effects of the micellar solubilisation on the reactivity of the preservative have been elucidated by NMR and UV spectroscopies. The presence of MP reduces the critical micelle temperature (CMT) of any of the poloxamines and induces the formation of larger micelles at room temperature compared to the plain poloxamines; in addition, a remarkable temperature dependent effect on the structure of the micelles has been detected, which progressively evolve from core-shell spheres to rods as the temperature increases. The incorporation of the preservative into the micelles modifies its reactivity against alkaline hydrolysis, resulting in a decrease of its reaction rate constant in which the dominant factor for the reduction in the hydrolysis rate is the incorporation into the micelle core, with a little effect of the length of the hydrophilic polyethylene oxide (PEO) blocks.
Autores: Fujiyoshi Tamae, Takeo; Carrez, O.; Imizcoz, M.; et al.
ISSN 0144-8617  Vol. 219  2019  págs. 105 - 112
Interpenetrating polymer network (IPN) hydrogels were synthesised using beta-cyclodextrin (beta-CD) and N-vynil-2-pyrrolidone (NVP) crosslinked with epichlorohydrin and divinylbenzene, respectively, and prepared by four different procedures: simultaneous, sequential, hybrid and a novel one named hybrid-sequential. The IPNs prepared have been characterised by infrared spectroscopy and thermal analysis. The equilibrium swelling in water and the sorption of model substances into the IPNs have also been studied. The model sorbates (1-naphthol, 2-acetylnaphthalene and tannic acid) were selected according to the affinities towards each one of the two constituent polymers. Our studies reveal that these IPNs can be applied for the sorption of substances that can interact with the network by two mechanisms, i.e. inclusion within cyclodextrin cavities and/or via specific interactions with the functional groups present. Besides, due to the complementary character of their constituent polymers, these networks could also serve to retain two substances of different nature such as cetirizine and pseudoephedrine.
Autores: García-Padial Alonso, Marcos; Martínez Oharriz, María Cristina; Isasi Allica, José Ramón; et al.
ISSN 0021-8561  Vol. 65  Nº 24  2017  págs. 4905 - 4910
The sorption and release of tyrosol and caffeic acid, two biophenolic antioxidants with known health benefits, in different insoluble cyclodextrin polymers have been studied. Cyclodextrin polymers were synthesized by cross-linking, beta-cyclodextrin or 50:50 w/w nominal mixtures of alpha- and beta-cyclodextrins using either epichlorohydrin (EP) or toluene-2,4-diisocyanate (TDI) as cross-linking agents. An analogous sucrose polymer was prepared using EP as cross-linking reagent. Freundlich isotherms and isosteric heats of sorption for tyrosol and caffeic acid in the insoluble beta-cyclodextrin polymer cross-linked with epichlorohydrin at 50 degrees C were obtained and discussed. Finally, the release of tyrosol and caffeic acid has been studied from loaded polymer disks, the microstructures of which were characterized by mercury intrusion porosimetry. Caffeic acid shows greater affinity than tyrosol for the polymeric matrices as it presents a higher sorption and a lower and slower release. However, tyrosol has a higher isosteric heat of sorption for low coverages.
Autores: González Gaitano, Gustavo; Isasi Allica, José Ramón; Vélaz Rivas, Itziar; et al.
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: Lucio Ollauri, David; Zornoza Cebeiro, Arantza; Martínez Oharriz, María Cristina
ISSN 0378-5173  Vol. 467   Nº 1 - 2  2014  págs. 19 - 26
The interactions of diflunisal (DF) with chitosans (CS) of different molecular weights and carboxymethylchitosan (CMCS), a water-soluble derivative, have been investigated. The interactions in solution have been studied by solubility assays in which the highest solubilisation (13-fold) was obtained with CMCS. Solid dispersions were prepared by coevaporation and kneading methods. Solid state characterisation was performed by X-ray diffraction analysis, scanning electron microscopy, thermomicroscopy, differential thermal analysis and infrared spectroscopy. Drug-polymer electrostatic interactions and hydrogen bonds are the main binding forces in these systems. The kneading method gave rise to amorphous systems regardless of the polymer employed. However, coevaporation resulted in the formation of different polymorphs of diflunisal (form II or III) depending on the type of polymer used. Therefore, it seems that drug-polymer interactions determine the crystallization pattern of the drug. Finally, diflunisal release from these systems improved markedly with CMCS and significantly in the presence of low molecular weight CS.
Autores: García-Padial Alonso, Marcos; Martínez Oharriz, María Cristina; Isasi Allica, José Ramón; et al.
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: García-Padial Alonso, Marcos; Martínez Oharriz, María Cristina; Navarro Blasco, Íñigo; et al.
ISSN 0021-8561  Vol. 61  Nº 50  2013  págs. 12260 - 122604
Tyrosol and caffeic acid are biophenols that contribute to the beneficial properties of virgin olive oil. The influence of hydroxypropyl-beta-cyclodextrin (HP beta-CD) on their respective antioxidant capacities was analyzed. The ORAC antioxidant activity of tyrosol (expressed as mu M Trolox equivalents/mu M Tyrosol) was 0.83 +/- 0.03 and it increased up to 1.20 +/- 0.11 in the presence of 0.8 mM HP beta-CD. However, the ORAC antioxidant activity of caffeic acid experienced no change. The different effect of HP beta-CD on each compound was discussed. In addition, the effect of increasing concentrations of different cyclodextrins in the development of ORAC-fluorescence (ORAC-FL) assays was studied. The ORAC signal was higher for HP beta-CD, followed by M beta-CD, beta-CD, gamma-CD and finally alpha-CD. These results could be explained by the formation of inclusion complexes with fluorescein.
Autores: Maddens, T.; Vélaz Rivas, Itziar; Machín Ledesma, Rubén; et al.
ISSN 1388-3127  Vol. 70  Nº 3 - 4  2011  págs. 415 - 419
Complexation of ebastine (EB) with hydroxypropyl and methyl-beta-cyclodextrin (HP-beta-CD and Me-beta-CD) was studied in aqueous solutions and in the solid state. The formation of inclusion complexes in aqueous solutions was analysed by the solubility method. The assays were designed using low CD concentrations compared with the solubility of these derivatives in order to avoid non-inclusion phenomena and to obtain a linear increase in EB solubility as a function of CD concentration. The values of complexation efficiency for HP-beta-CD and Me-beta-CD were 1.9 x 10(-2) and 2.1 x 10(-2), respectively. It seems that the non polar character of the methyl moiety slightly favoured complexation. In relation to solid state complexation, 1: 1 EB: CD systems were prepared by kneading, and by heating a drug-CD mixture at 90 degrees C. They were analysed using X ray diffraction analysis by comparison with their respective physical mixtures. A complex with a characteristic diffraction pattern similar to that of the channel structure of beta-CD was formed with Me-beta-CD in 1: 1 melted and 1: 2 EB: CD kneaded systems. Complexation with HP-beta-CD was not clearly evidenced because only a slight reduction of drug crystallinity was detected. Finally, the loading of EB in two beta-CD polymers cross-linked with epichlorohydrin yielded 7.3 and 7.7 mg of EB/g polymer respectively.
Autores: Uzqueda Garde, Maite; Zornoza Cebeiro, Arantza; Isasi Allica, José Ramón; et al.
ISSN 1388-3127  Vol. 69  Nº 3 - 4  2011  págs. 469 - 474
beta-cyclodextrin insoluble polymers (beta CDP), a type of hydrogels with a high swelling capacity, can be obtained by crosslinking beta-cyclodextrin (beta CD) with epichlorohydrin. Terbinafine (TB) is an oral and topical antifungal drug that can be housed into the cavity of beta-cyclodextrin, so it seems probable that the drug could interact with the insoluble beta CDP. Different organic molecules can be sorbed on the polymer network and also included within the beta CD cavities, so these hydrogels have potential applications in the pharmaceutical field as drug carriers. In this work, the sorption of TB on beta CDP and the optimal conditions to load the polymer with the drug were studied. Sorption kinetics and Freundlich isotherms of TB on beta CDP at 25A degrees C were obtained and the influence of several parameters on the sorption process of TB was investigated. It was found that a high initial concentration of drug, high TB:beta-CD molar ratios and low ionic strengths were the most favourable conditions. No significant influence of temperature was observed. Moreover, the sorption kinetic profile obtained for terbinafine was compared to that of naftifine, another antifungal agent of similar structure. Terbinafine presented higher affinity for the polymer, according to the higher stability constant of the drug-beta CD inclusion complex. In relation to the release studies from the loaded polymer, 0.1 M HCl was the most favourable medium to allow the release of the drug.
Autores: Fernández, L.; Machín Ledesma, Rubén; Zornoza Cebeiro, Arantza; et al.
ISSN 1388-3127  Vol. 69  Nº 3-4  2011  págs. 411 - 415
The mechanisms of sorption and release of solutes from polymeric materials synthesised by cross-linking ß-cyclodextrin (ß-CD) with epichlorohydrin have been investigated. Gemfibrozil (pKa 4.7) was chosen as model solute. The polymers were obtained by suspension (P1) and block polymerisation (P2). Both P1 and P2 had similar ß-CD contents (65 and 64%) and their swelling capacities were 5.0 and 5.8 cm3/g, respectively. The sorption of gemfibrozil kinetic data in water and in aqueous solutions at pH 2.8 and 7.0 were fitted to a hyperbolic equation and they were studied by applying the Weber and Morris and the Elovich equations. P2 presented faster rates and higher sorption capacities in water and at pH 2.8. The mechanisms of sorption were pH-dependent. In water, the sorption rate was determined by the diffusion of gemfibrozil in the polymer network and fitted the Weber and Morris equation. At pH 2.8 a better adjustment to the Elovich equation suggested a significant influence of the inclusion in the ß-CD cavities. The release kinetics at pH 7.0 was controlled by drug solubilisation and presented maximum release values of 90 (P1) and 95% (P2), with a suitable regeneration of the loaded polymer. In water, the release was slower, fitted a hyperbole and the mechanism was controlled by drug solubility and also by the polymeric geometry. Finally, release assays were carried out from discs of loaded polymer in a medium that simulated the gastrointestinal tract.
Autores: Uzqueda Garde, Maite; Martín Bachiller, Carmen; Zornoza Cebeiro, Arantza; et al.
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.