Tommasina Coviello

Hyaluronic acid and dextran-based semi-IPN hydrogels as biomaterials for bioprinting.

Bioprinting is a recent technology in tissue engineering used for the design of porous constructs through layer-by-layer deposition of cell-laden material. This technology would benefit from new biomaterials that can fulfill specific requirements for the fabrication of well-defined 3D constructs, such as the preservation of cell viability and adequate mechanical properties. We evaluated the suitability of a novel semi-interpenetrating network (semi-IPN), based on hyaluronic acid and hydroxyethyl-methacrylate-derivatized dextran (dex-HEMA), to form 3D hydrogel bioprinted constructs. The rheological properties of the solutions allowed proper handling during bioprinting, whereas photopolymerization led to stable constructs of which their mechanical properties matched the wide range of mechanical strengths of natural tissues. Importantly, excellent viability was observed for encapsulated chondrocytes. The results demonstrate the suitability of hyaluronic acid/dex-HEMA semi-IPNs to manufacture bioprinted constructs for tissue engineering.

Preparation and properties of new unilamellar non-ionic/ionic surfactant vesicles

Abstract Non-ionic surfactant vesicles (NSVs) were prepared from polysorbate 20 and cholesterol by means of two different methods: by direct sonication of an aqueous dispersion of the various components (bulk) or by solubilization of the components, evaporation of the organic solvent to form a film inside the vessel used for the preparation and then by sonication (film). The influence of the preparation technique on the properties of the obtained structures was studied. Vesicles with bigger dimensions and higher entrapment efficiency were obtained when sonication was carried out after the film formation. Vesicle formation in the presence of ionic surfactants was investigated in order to evaluate the effect of charged components on vesicle dimensions, entrapment efficiency and stability. Dimethyldioctadecylammonium bromide (DDOA) and cetylpyridinium chloride (CPy) were used to introduce a positive charge in the vesicle structure, while dicetylphosphate (DCP) was used for a negative charge. Better resistance to osmotic stress and higher entrapment efficiency values were obtained with vesicles containing DCP and CPy.

Comparative analysis of the behavior of gellan gum (S-60) and welan gum (S-130) in dilute aqueous solution☆

Abstract Optical rotation, circular dichroism, and microcalorimetric data clearly and consistently show that gellan gum, S-60 (Me 4 N + form), undergoes in water at 25° a rather sharp conformational transition upon increasing the concentration of added Me 4 NCl. Similar data show that S-60 behaves anomalously upon addition of Ca 2+ ions with, eventually, formation of aggregates and/or gels. The Me 4 NCl-induced conformational change of S-60 is thermally reversible with no hysteresis. In contrast, with welan gum, S-130 (Me 4 N + form), no evidence could be found for a dependence of chain conformation of the main external variables considered. Comparison of the circular-dichroism spectra of the two polysaccharides suggests that S-130 in water might be present in a stiff conformation similar to that assumed by S-60 in aqueous Me 4 NCl.

Scleroglucan: A Versatile Polysaccharide for Modified Drug Delivery

Scleroglucan is a natural polysaccharide, produced by fungi of the genus Sclerotium, that has been extensively studied for various commercial applications (secondary oil recovery, ceramic glazes, food, paints, etc.) and also shows several interesting pharmacological properties. This review focuses its attention on the use of scleroglucan, and some derivatives, in the field of pharmaceutics and in particular for the formulation of modified-release dosage forms. The reported investigations refer mainly to the following topics: natural scleroglucan suitable for the preparation of sustained release tablets and ocular formulations; oxidized and crosslinked scleroglucan used as a matrix for dosage forms sensitive to environmental conditions; co-crosslinked scleroglucan/gellan whose delivery rate can be affected by calcium ions. Furthermore, a novel hydrogel obtained with this polysaccharide and borate ions is described, and the particular structure of this hydrogel network has been interpreted in terms of conformational analysis and molecular dynamics. Profound attention is devoted to the mechanisms involved in drug release from the tested dosage forms that depend, according to the specific preparation, on swelling and/or diffusion. Experimental data are also discussed on the basis of a mathematical approach that allows a better understanding of the behavior of the tested polymeric materials.

Preparation and Characterization of Novel Gellan Gum Hydrogels Suitable for Modified Drug Release

Innovative hydrogels obtained by physical and chemical crosslinking of deacylated Gellan gum have been characterized in terms of water uptake, rheological properties and compressibility, and the behaviour of the tested materials, according to the type of the obtained network, is thoroughly discussed. The release from the various gels of loaded model molecules of different steric hindrance was also investigated and the trend of the release profiles has been related to the structures proposed for the physical and the chemical hydrogel.

Drug delivery strategies using polysaccharidic gels

Hydrogels are hydrophilic polymeric networks, with chemical or physical crosslinks, that are capable of swell and can retain a large amount of water. Among the numerous types of macromolecules that can be used for hydrogel formation, polysaccharides show very attractive advantages in comparison to synthetic polymers. They are widely present in living organisms, are usually abundant and show a number of peculiar physicochemical properties; furthermore, these macromolecules are, in most cases, non-toxic, biocompatible and can be obtained from renewable sources. For these reasons, polysaccharides seem to be particularly suitable for different applications in the wide field of pharmaceutics. As examples of the studies that have been carried out on this topic, this review will focus on two polysaccharides, alginate and xyloglucan. Alginate has been, and still is, extensively investigated and has numerous industrial applications, whereas xyloglucan was chosen because, although it has been much less studied, it shows interesting properties that should find important practical uses in the near future. The possible advantages of physical gels over those that are chemically crosslinked are also discussed.

A novel co-crosslinked polysaccharide: studies for a controlled delivery matrix

The formulation of a new controlled delivery system, based on a novel type of matrix obtained by the chemical reaction carried out in an aqueous medium on a mixed physical gel of gellan and scleroglucan, is described in this paper. The preparation yielded a new co-crosslinked polysaccharide (CCP) hydrogel, bearing carboxylic groups, that showed a sustained release behaviour that can be modulated by means of calcium ions. For the characterization of CCP, diffusion experiments through the swelled hydrogel were carried out in different environmental conditions and the release from tablets prepared with CCP and a model drug was evaluated. The addition of CaCl2 in the formulation of the dosage forms allowed a further marked reduction in delivery rate to be obtained; this effect is to be related to the free ionized carboxylic groups still present in the gellan moiety of CCP. The different behaviour of Ca+2 and Na+ ions is discussed.

Structural and rheological characterization of Scleroglucan/borax hydrogel for drug delivery

The polysaccharide Scleroglucan, one of the most rigid polymers found in nature, can form a chemical/physical gel, in the presence of borax. The obtained hydrogel was loaded with three different model molecules (Theophylline, Vitamin B12 and Myoglobin) and then, after freeze-drying, was used as a matrix for tablets. The release profiles of the substances from the dosage forms were evaluated; the matrix appeared capable to modulate the diffusion of the chosen molecules, and different diffusion rates were observed, according to the different radii of the tested molecules. Interestingly, in the dissolution medium the matrix undergoes an anisotropic swelling taking place only in the axial direction, while a negligible radial variation occurs. The water uptake of the matrix occurs according to a Fickian process. Samples at two different polymer concentrations (0.7 and 2.3%, w/v) were characterized in terms of rheological and mechanical parameters and the properties were interpreted in terms of the molecular structure obtained by conformational analysis. The flow curves acquired in the viscoelasticity interval, show the effect of the borate ion in improving the resistance of the gel in comparison to the polymer alone. The evaluation of the moduli indicates that the system is viscoelastic, with an appreciable liquid component that increases as the polymer concentration decreases. Also the cohesion of the gel is higher in comparison to the Scleroglucan and is strongly dependent on temperature. The combination of experimental and theoretical conformational analysis approaches, allowed us to propose a model for the structure of the macromolecular network and to give an explanation to the anomalous swelling that was observed. It came out that the polymer can built up a channel structure, mediated via borax ion interaction, that can accommodate guest molecules of different size.

Novel hydrogel system from scleroglucan: synthesis and characterization

New hydrogels obtained by a crosslinking reaction between the polycarboxylated derivative of scleroglucan (sclerox) and 1, 6-hexanedibromide have been prepared and characterized. Different ratios between the alkane dihalide and sclerox yielded products with appreciably different properties. Water uptake by the hydrogel with a low degree of crosslinking was remarkably affected by ionic strength. The diffusion of a model molecule (theophylline) through the swelled crosslinked polymers was studied and the theoretical analysis leading to the calculation of permeability coefficients in different environmental conditions is reported. Tablets prepared with one of the new hydrogels behaved as swellable monolithic systems suitable for sustained drug release.

Scleroglucan/borax: characterization of a novel hydrogel system suitable for drug delivery

A new hydrogel, with scleroglucan using borax as a crosslinker, has been prepared. The physical gel has been loaded with a model molecule (theophylline) and the release of the drug from the gel was evaluated. The same system was used to prepare tablets and the delivery of theophylline in different environmental conditions (HCl and SIF) was determined. A recent theoretical approach has been applied to the dissolution profiles obtained from the tablets and a satisfactory agreement has been found with the experimental data. Furthermore, the diffusion coefficient of the model molecule was evaluated according to a suitable strategy that was tested on two set of data obtained with different set-ups (permeation and diffusion experiments). A simplified mathematical approach allows to reduce the two-dimensional problem of the Ficks second law in a one-dimensional system leading to a much easier handling of the data without loosing the accuracy of the original problem in two dimensions. The characterization of the gel has been also carried out following the kinetics of swelling in terms of water uptake.