Leyre Pérez-Álvarez

Biodegradable chitosan nanogels crosslinked with genipin.

Chitosan nanoparticles crosslinked with genipin were prepared by reverse microemulsion that allowed to obtain highly monodisperse (3-20 nm by TEM) nanogels. The incorporation of genipin into chitosan was confirmed and quantitatively evaluated by UV-vis and (1)H NMR. Loosely crosslinked chitosan networks showed higher water solubility at neutral pHs than pure chitosan. The hydrodynamic diameter of the genipin-chitosan nanogels ranged from 270 to 390 nm and no remarkable differences were found when the crosslinking degree was varied. The hydrodynamic diameters of the nanoparticles increased slightly at acidic pH and the protonation of ionizable amino groups with the pH was confirmed by the zeta potential measurements. The biocompatible and biodegradable nature, as well as the colloidal and monodisperse particle size of the prepared nanogels, make them attractive candidates for a large variety of biomedical applications.

Water soluble folate-chitosan nanogels crosslinked by genipin

Folate-chitosan conjugates were prepared by a concurrent functionalization and crosslinking reaction with the natural crosslinker genipin. Genipin molecule was employed simultaneously as crosslinker agent and spacer molecule in order to allow the functionalization with folic acid for active tumor targeting. The reaction was carried out in reverse microemulsion which provided colloidal size and monodisperse particle size distribution. The water solubility of the obtained folate-genipin-chitosan nanogels was studied as function of the pH of the medium and all nanoparticles were totally dispersible at physiological pH. The enzymatic degradability of the nanogels in a lysozyme solution was evaluated at acidic and physiological pH. QELS analyses of the swelling behavior of the nanogels with the pH did not show a clear pH-sensitivity. However, the study on the loading and release capacity of 5-fluorouracil revealed an interesting pH-responsive behavior of the nanogels that makes them promising as nanodevices for targeted anticancer drug delivery.

Preparation and characterization of soluble branched ionic β-cyclodextrins and their inclusion complexes with triclosan

This study aims to synthesize, characterize and investigate the water solubility and cytotoxicity of branched anionic/cationic β-cyclodextrins (bβCDs) obtained by reaction with epichlorohydrin and chloroacetic acid or choline chloride, respectively, by a single step polycondensation reaction. Obtained ionic bβCDs were investigated as an attempt to comparatively study anionic and cationic bβCDs. Water solubility of both ionic derivatives was similar (400 mg/mL) at neutral and basic pHs and remarkably higher than that of their neutral homologues. Additionally, a pH-dependent solubility of anionic bβCDs was observed. Cytotoxicity of ionic bβCDs was evaluated on Human colon carcinoma Caco-2 cells and high cell viability (>99%) was observed in the range of 0-100 mg/mL for anionic and cationic samples, in the same range of that of neutral and parent β-CDs. Additionally, complexes formation capacity with triclosan, a poor water soluble antimicrobial agent, was confirmed by several techniques observing a complexation limit around 4 mg/mL for both systems and higher stability constant for anionic bβCDs than cationic derivatives.

Branched and ionic β-Cyclodextrins multilayer assembling onto polyacrylonitrile membranes for removal and controlled release of triclosan

The present study summarizes the formation and characterization of multilayers of polyacrylonitrile (PAN) membranes with β-cyclodextrin derivatives in order to be potentially interesting for triclosan (TR) controlled delivery with antibacterial purposes, as well as, for the removal of TR from wastewater. With this object, cationic and anionic branched β-cyclodextrins (bβCDs) were incorporated by layer-by-layer (LbL) process onto previously synthesized and hydrolyzed PAN membranes. FTIR, XPS and labelling with fluoresceinamine (FA) let to study the formation and stability of the prepared multilayered systems. TR is a widely used antibacterial and antifungal agent with proven ability to inhibit bacterial growth that, however, recently has shown a potential toxicity. The ability of obtained bβCDs/PAN multilayered membranes to retain TR in water was evaluated by two different loading procedures. The delivery kinetic profile of TR from loaded membranes was also analyzed showing the maximum release in the first 24h.

Construction of antibacterial poly(ethylene terephthalate) films via layer by layer assembly of chitosan and hyaluronic acid

Polyelectrolytic multilayers (PEMs) with enhanced antibacterial properties were built up onto commercial poly(ethylene terephthalate) (PET) films based on the layer by layer assembling of bacterial contact killing chitosan and bacterial repelling highly hydrated hyaluronic acid. The optimization of the aminolysis modification reaction of PET was carried out by the study of the mechanical properties and the surface characterization of the modified polymers. The layer by layer assembly was successfully monitored by TEM microscopy, surface zeta-potential, contact angle measurements and, after labeling with fluorescein isothiocyanate (FTIC) by absorption spectroscopy and confocal fluorescent microscopy. Beside, the stability of the PEMs was studied at physiological conditions in absence and in the presence of lysozyme and hyaluronidase enzymes. Antibacterial properties of the obtained PEMs against Escherichia coli were compared with original commercial PET.

Active Release Coating of Multilayer Assembled Branched and Ionic β-Cyclodextrins onto Poly(ethylene terephthalate)

Branched ionic cyclodextrins multilayers were assembled onto the surface of previously aminolyzed poly(ethylene terephthalate) in order to construct local drug delivery tailored platforms with potential applicability as materials for indwelling medical devices. The construction of the multilayers took place by the alternate deposition of ionic cyclodextrin derivatives and was characterized by surface zeta-potential measurements, X-ray photoelectron spectroscopy and, after fluorescent labeling of anionic branched cyclodextrins, by UV-vis spectroscopy and confocal fluorescence spectroscopy. Transmission electron microscopy is used for the first time to show the deposited coating, and an average thickness of ∼270nm for 20 bilayered covering was measured. Contact angle measurements showed great differences in the films as the number of cyclodextrin layers was increased, and highly hydrophilic (19.7±1.5° for 10 bilayers) surfaces were obtained. The loading and release capacity of the antimicrobial triclosan, as hydrophobic model molecule, from PET coated surfaces was also studied.

Poly(L-lactide)/branched β-cyclodextrin blends: Thermal, morphological and mechanical properties

In this work we develop poly(L-lactide)/branched β-cyclodextrin (bβCD) blends in an attempt to obtain new biocompatible and biodegradable materials to be used in the emerging fields of pharmaceutical, biomedicine and food industry. Ionic branched β-cyclodextrin (bβCD) was obtained by polycondensation of the β-CD monomer and it was blended with a commercially available PLLA. Fourier transform infrared spectroscopy (FTIR) has been applied to study the occurring interactions between both partners. Thermal properties of blends have been analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), while the phase structure of the blends was analyzed by scanning electron microscopy (SEM). Finally, dynamic mechanical analysis (DMA) has been used to provide further insights into the features controlling miscibility between PLLA and bβCD. Results show the presence of a single phase irrespectively of the blend composition. Overall, this work opens new perspectives for the development of naturally available materials with tunable functional properties for applications in which cyclodextrins emerge as a new class of promising candidates.

U-Shaped and Surface Functionalized Polymer Optical Fiber Probe for Glucose Detection

In this work we show an optical fiber evanescent wave absorption probe for glucose detection in different physiological media. High selectivity is achieved by functionalizing the surface of an only-core poly(methyl methacrylate) (PMMA) polymer optical fiber with phenilboronic groups, and enhanced sensitivity by using a U-shaped geometry. Employing a supercontinuum light source and a high-resolution spectrometer, absorption measurements are performed in the broadband visible light spectrum. Experimental results suggest the feasibility of such a fiber probe as a low-cost and selective glucose detector.

Covalently and Ionically Crosslinked Chitosan Nanogels for Drug Delivery.

Chitosan nanogels present a very interesting combination of valuable characteristics for drug delivery; those derived from their nanometric size, such as, large surface area, rapid stimuli-response, and easy functionalization; and those emerged especially from their biocompatibility, biodegradability and mucoadhesive nature. Due to this, chitosan nanogels have reached a prominent position as nanocarriers and have originated accelerated research worldwide. Diverse methods to prepare chitosan nanogels have been reported, showing a dependence on final swelling, drug encapsulation capability and release properties with different synthesis variables, in such a way that they can be exploited to be modulated. The present review describes the properties of chitosan nanogels, along with the different methods of crosslinking and confining chitosan in nanosized particles, and the various fields of drug delivery where they have been applied. This work aims to emphasize the connection between the characteristics of chitosan and the synthetic variables with the final properties of chitosan nanogels in order to enhance controlled drug loading and a sustained release.

Polysaccharide-Based Superabsorbents: Synthesis, Properties, and Applications

Traditional absorbent hydrogels are based on the copolymerization of petroleumbased synthetic vinyl monomers such as acrylic acid, methacrylic acid, and acrylamide derivatives. Nevertheless, these materials are usually expensive, poorly degradable, and non-environmentally friendly. On the contrary, natural polysaccharides display significant advantages such as availability, low production cost, nontoxicity, biocompatibility, and biodegradability. Accordingly, polysaccharides emerge as an interesting sustainable alternative to traditionally employed polymers. In addition, polysaccharides can easily form hydrogels by chemical or physical crosslinking (including hydrogen bonding and ionic interactions) or a combination of both, which makes the crosslinking of natural polysaccharides a versatile and promising approach for superabsorbent hydrogel (SAH) production. Therefore, in the last years, numerous polysaccharides including starch, cellulose, alginate, chitosan, and guar gum, among others, have been employed in SAH fabrication. Polysaccharide-based SAHs have been used in agriculture, hygiene products, waste treatment, crack mitigation in building applications, tissue engineering, and controlled release, for biomedical and soil conditioning applications. Despite of the evident commercial and environmental advantages of polysaccharide-based SAHs, they also display some drawbacks that make them continue appearing as a challenge research field. In this sense, although the biodegradability of polysaccharide-based hydrogels is a key characteristic for some applications because it avoids pollution-related issues and enables enhanced controlled release, at the same time, it could delay the development of longtime sustained release systems. Moreover, polysaccharide crosslinking leads to hydrogels with poor mechanical stability which is another associated disadvantage of these types of materials that needs to be overcome. Therefore an increasing amount of investigations about new synthetic approaches to improve the properties of polysaccharide-based hydrogels have been reported in the last years. In this chapter, the recent progress of this type of hydrogels is reviewed. The synthetic methods employed to obtain SAHs from the most common polysaccharides and the main properties of these materials with a special emphasis on swelling and mechanical properties are studied. Furthermore, the applications of SAHs have been summarized highlighting the most outstanding and promising uses.