Pietro Matricardi

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.

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.

Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

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.

In situ forming IPN hydrogels of calcium alginate and dextran-HEMA for biomedical applications

In situ forming hydrogels, which allow for the modulation of physico-chemical properties, and in which cell response can be tailored, are providing new opportunities for biomedical applications. Here, we describe interpenetrating polymer networks (IPNs) based on a physical network of calcium alginate (Alg-Ca), interpenetrated with a chemical one based on hydroxyethyl-methacrylate-derivatized dextran (dex-HEMA). IPNs with different concentration and degree of substitution of dex-HEMA were characterized and evaluated for protein release as well as for the behavior of embedded cells. The results demonstrated that the properties of the semi-IPNs, which are obtained by dissolution of dex-HEMA chains into the Alg-Ca hydrogels, would allow for injection of these hydrogels. Degradation times of the IPNs after photocross-linking could be tailored from 15 to 180 days by the concentration and the degree of substitution of dex-HEMA. Further, after an initial burst release, bovine serum albumin was gradually released from the IPNs over approximately 15 days. Encapsulation of expanded chondrocytes in the IPNs revealed that cells remained viable and, depending on the composition, were able to redifferentiate, as was demonstrated by the deposition of collagen type II. These results demonstrate that these IPNs are attractive materials for pharmaceutical and biomedical applications due to their tailorable mechanical and degradation characteristics, their release kinetics and biocompatibility.

In situ cross-linkable novel alginate-dextran methacrylate IPN hydrogels for biomedical applications: mechanical characterization and drug delivery properties.

In situ polymerizable hydrogels are extensively investigated to implement new biomedical and pharmaceutical approaches. In the present paper a novel polysaccharidic matrix based on calcium alginate (Ca(II)-Alg) hydrogel and dextran methacrylate derivative (Dex-MA), showing potential applicability in the field of pharmaceutics is described. The semi-interpenetrating polymer system (semi-IPN) obtained by a dispersion of Dex-MA chains into a Ca(II) hydrogel leads to a hydrogel with rheological properties quite different from those of Ca(II)-Alg, allowing to inject the semi-IPN easily through an hypodermic needle. The UV curing of the semi-IPN, by cross-linking of the methacrylate moieties, leads to an IPN strong hydrogel that can be used for a modulated delivery of bioactive molecules. In the present paper, rheological and mechanical behaviors of the semi-IPN and of the IPN are discussed. The release of model molecules, including a protein, are also presented to show the suitability of the novel system as a drug delivery system.

Characterization of polysaccharide hydrogels for modified drug delivery.

Hydrogels are hydrophilic macromolecular networks that are capable of retaining a large amount of water. A precise description of these systems is actually quite complex and the practical use of hydrogels for drug delivery and biomedical applications is often not supported by a well-defined knowledge of the overall structure of the polymeric network. In this paper, we report the characterization of two different systems: a chemical network based on Guar Gum (GG) and a physical gel prepared with Xanthan (Xanth) and Locust Bean Gum (LBG). The dynamo-mechanical properties of the gels were analysed: the cohesiveness and the adhesion of the networks were strongly dependent on time, temperature, and composition. The kinetics of the chemical crosslinking was followed by means of rheological measurements, i.e. recording the mechanical spectra of the gelling system, and the power law exponent at the gel point was evaluated. Furthermore, the networks, loaded with model drugs with different steric hindrance, were used as matrices for tablets and the rate of release of such model drugs was studied. The diffusion of the guest molecules was deeply dependent on their dimensions; in the case of Xanth–LBG tablets the release profiles were almost independent from the different cohesion properties of the starting hydrogel composition.

Liposomes Coated with Chitosan-Xanthan Gum (Chitosomes) as Potential Carriers for Pulmonary Delivery of Rifampicin

The aim of this work was to develop new microparticles for drug delivery to lungs by coating liposomes with chitosan (CH)-xanthan gum (XG) polyelectrolyte complexes to obtain chitosomes. To this purpose, two groups of liposomes were prepared using a mixture of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine in two different concentrations to evaluate their capability to entrap appropriate amounts of the model drug rifampicin. The obtained vesicles were then coated with different CH-XG weight ratios and liposomes and chitosomes were characterized in terms of morphology, size, size distribution, zeta potential, drug entrapment, and rheological properties. The efficiency of chitosomes and liposomes during nebulization was also studied. Results of this study indicated that nebulization and rheological properties of chitosomes are affected by the CH-XG weight ratio. In particular, CH-XG 1:0.5 (w/w) coating was able to greatly improve drug total mass output and drug deposition in the lower stages of the impinger.

Gelation of chemically cross-linked polygalacturonic acid derivatives

We have previously developed a process for the cross-linking of glycuronans (tetrabutylammonium, TBA, salt form) with dialkyl or dialkylaryl halides. In the present work we have investigated the effect of such cross-linkers, including 1,6-dibromohexane (DBH), 1,3-diiodopropane and 1,10-diiododecane on TBA polygalacturonic acid (PGA). In particular, we have employed PGADBH at low stoichiometric amounts (R) of DBH so that the cross-linking reaction reaches an equilibrium conversion either just above or below the gel point conversion. At R = 0.084 a clear power law region is seen in both shear dynamic moduli G′ and G″, and with frequency exponents of 0.657 for G″ and 0.640 for G′ (both ± 0.004), a condition which has been associated with the gel point. We have also investigated the effect of the other cross-linking agents to assess the significance of different halogenic and chain length effects.