Loredana Tammaro

Transport Properties of Water Vapor in Polylactide/Montmorillonite Nanocomposites

Abstract Both intercalated and exfoliated poly(L‐lactide) (PLA) layered aluminosilicate nanocomposites were synthesized and characterized in terms of barrier properties. Intercalated polylactide/montmorillonite nanocomposites were obtained by melt blending PLA and a montmorillonite modified with bis‐(2‐hydroxyethyl)methyl (tallowalkyl) ammonium cations (MMT) (1, 3, 5, and 10 wt/wt%). A sample containing 3 wt% of MMT was prepared with 20 wt% of PEG1000 as plasticizer. Exfoliated nanocomposite containing 3 wt% of MMT was synthesized by in situ coordination‐insertion ring‐opening polymerization of L,L‐lactide, after adequate activation of the primary hydroxyl groups functionalizing the organo‐modifier. The barrier properties were studied for water vapor at 30°C. The sorption (S) and the zero‐concentration diffusion coefficient (D 0) were evaluated. The sorption curves of water vapor in all the samples follow the dual‐sorption behavior. The amount of solvent absorbed derived from the linear part of the curve appears lower in the intercalated nanocomposites for all studied MMT content than for the exfoliated sample. The thermodynamic diffusion parameters, D 0, decreased by one order of magnitude with increasing MMT content from 0 to 10 wt% in the intercalated samples. In comparison with the value of D 0 for the parent unfilled PLA, the intercalated samples containing 3 wt% of MMT (with or without PEG 1000) were found to be slightly lower. On the other hand, the exfoliated nanocomposite showed strong deviation in the D 0 value, being lower by about two orders of magnitude with respect to the results obtained for all the other samples (unfilled and intercalated). The exfoliation of the inorganic component in the continuous polymeric phase seems to be the most important factor to improve the barrier properties of the material to water vapor.

Encapsulation of diclofenac molecules into poly (ε caprolactone) electrospun fibers for delivery protection

Mg-Al Hydrotalcite-like clay (LDH) intercalated with diclofenac anions (HTlc-DIC) was introduced into poly(e-caprolactone) (PCL) in different concentrations by the electrospinning technique, and mats of nonwoven fibers were obtained and compared to the pristine pure electrospun PCL. The fibers, characterized by X-ray diffraction, thermogravimetric analysis, and differential scanning calorimetry, show an exfoliated clay structure up to 3 wt%, a good thermal stability of the diclofenac molecules and a crystallinity of PCL comparable to the pure polymer. The scanning electron microscopy revealed electrospun PCL and PCL composite fibers diameters ranging between 500nm to 3.0 µm and a generally uniform thickness along the fibers. As the results suggested the in vitro drug release from the composite fibers is remarkably slower than the release from the corresponding control spun solutions of PCL and diclofenac sodium salt. Thus, HTlc-DIC/PCL fibrous membranes can be used as an antinflammatory scaffold for tissue engineering.

Modified hydrotalcite-like compounds as active fillers of biodegradable polymers for drug release and food packaging applications

This review treats the recent patents and related literature, mainly from the Authors laboratories, on biomedical and food packaging applications of nano-composites constituted of biodegradable polymers filled with micro or nano crystals of organically modified Layered Double Hydroxides of Hydrotalcite type. After a brief outline of the chemical and structural aspects of Hydrotalcite-like compounds (HTlc) and of their manipulation via intercalation of functional molecular anions to obtain materials for numerous, sometime unexpected applications, the review approaches the theme in three separated parts. Part 1 deals with the synthetic method used to prepare the pristine Mg-Al and Zn-Al HTlc and with the procedures of their functionalization with anti-inflammatory (diclofenac), antibacterial (chloramphenicol hemisuccinate), antifibrinolytic (tranexamic acid) drugs and with benzoates with antimicrobial activity. Procedures used to form (nano) composites of polycaprolactone, used as an example of biodegradable polymer, and functionalized HTlc are also reported. Part 2 discusses a patent and related papers on the preparation and biomedical use of a controlled delivery system of the above mentioned pharmacologically active substances. After an introduction dealing with the recent progress in the field of local drug delivery systems, the chemical and structural aspects of the patented system constituted of a biodegradable polymer and HTlc loaded with the active substances will be presented together with an extensive discussion of the drug release in physiological medium. Part 3 deals with a recent patent and related papers on chemical, structural and release property of antimicrobial species of polymeric films containing antimicrobial loaded HTlc able to act as active packaging for food products prolonging their shelf life.

Electrospun fibers as potential carrier systems for enhanced drug release of perphenazine.

Solubility represents an important challenge for formulation of drugs, because the therapeutic efficacy of a drug depends on the bioavailability and ultimately on its solubility. Low aqueous solubility is one of the main issues related with formulation design and development of new molecules. Many drug molecules present bioavailability problems due to their poor solubility. For this reason there is a great interest in the development of new carrier systems able to enhance the dissolution of poorly water-soluble drugs. In this work, fibers containing an insoluble model drug and prepared by an electrospinning method, are proposed and evaluated to solve this problem. Two hydrophilic polymers, polyvinylpyrrolidone (Plasdone® K29/32) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used to increase the water solubility of perphenazine. The physico-chemical characterization suggests that the drug loaded in the fibers is in the amorphous state. Both polymeric carriers are effective to promote the drug dissolution rate in water, where this active pharmaceutical ingredient is insoluble, due to the fine dispersion of the drug into the polymeric matrices, obtained with this production technique. In fact, the dissolution profiles of the fibers, compared to the simple physical mixture of the two components, and to the reference commercial product Trilafon® 8mg tablets, show that a strong enhancement of the drug dissolution rate can be achieved with the electrospinning technique.

Adipose-derived stem cells cultivated on electrospun L-lactide/glycolide copolymer fleece and gelatin hydrogels under flow conditions - aiming physiological reality in hypodermis tissue engineering

INTRODUCTION Generation of adipose tissue for burn patients that suffer from an irreversible loss of the hypodermis is still one of the most complex challenges in tissue engineering. Electrospun materials with their micro- and nanostructures are already well established for their use as extracellular matrix substitutes. Gelatin is widely used in tissue engineering to gain thickness and volume. Under conventional static cultivation methods the supply of nutrients and transport of toxic metabolites is controlled by diffusion and therefore highly dependent on size and porosity of the biomaterial. A widely used method in order to overcome these limitations is the medium perfusion of 3D biomaterial-cell-constructs. In this study we combined perfusion bioreactor cultivation techniques with electrospun poly(l-lactide-co-glycolide) (P(LLG)) and gelatin hydrogels together with adipose-derived stem cells (ASCs) for a new approach in soft tissue engineering. METHODS ASCs were seeded on P(LLG) scaffolds and in gelatin hydrogels and cultivated for 24 hours under static conditions. Thereafter, biomaterials were cultivated under static conditions or in a bioreactor system for three, nine or twelve days with a medium flow of 0.3ml/min. Viability, morphology and differentiation of cells was monitored. RESULTS ASCs seeded on P(LLG) scaffolds had a physiological morphology and good viability and were able to migrate from one electrospun scaffold to another under flow conditions but not migrate through the mesh. Differentiated ASCs showed lipid droplet formations after 21 days. Cells in hydrogels were viable but showed rounded morphology. Under flow conditions, morphology of cells was more diffuse. DISCUSSION ASCs could be cultivated on P(LLG) scaffolds and in gelatin hydrogels under flow conditions and showed good cell viability as well as the potential to differentiate. These results should be a next step to a physiological three-dimensional construct for soft tissue engineering and regeneration.

Effect of layered double hydroxide intercalated with fluoride ions on the physical, biological and release properties of a dental composite resin

OBJECTIVES The aim of this work was the preparation of a new fluoride-releasing dental material characterized by a release of fluoride relatively constant over time without any initial toxic burst effect. This type of delivery is obtained by a matrix controlled elution and elicits the beneficial effect of a low amount of fluoride on human dental pulp stem cells (hDPSCs) towards mature phenotype. METHODS The modified hydrotalcite intercalated with fluoride ions (LDH-F), used as filler, was prepared via ion exchange procedure and characterized by X-ray diffraction and FT-IR spectroscopy. The LDH-F inorganic particles (0.7, 5, 10, 20wt.%) were mixed with a photo-activated Bis-GMA/TEGDMA (45/55wt/wt) matrix and novel visible-light cured composites were prepared. The dynamic thermo-mechanical properties were determined by dynamic mechanical analyzer. The release of fluoride ions in physiological solution was determined using a ionometer. Total DNA content was measured by a PicoGreen dsDNA quantification kit to assess the proliferation rate of hDPSCs. Alkaline phosphatase activity (ALP) was measured in presence of fluoride resins. RESULTS Incorporation of even small mass fractions (e.g. 0.7 and 5wt.%) of the fluoride LDH in Bis-GMA/TEGDMA dental resin significantly improved the mechanical properties of the pristine resin, in particular at 37°C. The observed reinforcement increases on increasing the filler concentration. The release of fluoride ions resulted very slow, lasting months. ALP activity gradually increased for 28 days in hDPSCs cell grown, demonstrating that low concentrations of fluoride contributed to the cell differentiation. CONCLUSIONS The prepared composites containing different amount of hydrotalcite filler showed improved mechanical properties, slow fluoride release and promoted hDPSCs cell proliferation and cell differentiation.

Fabrication, Physico-Chemical, and Pharmaceutical Characterization of Budesonide-Loaded Electrospun Fibers for Drug Targeting to the Colon

The objective of this study was to fabricate and characterize electrospun fibers loaded with budesonide with the aim of controlling its release in the gastrointestinal tract. Budesonide is a nonhalogenated glucocorticosteroid drug, highly effective in the treatment of some inflammatory bowel diseases with local action throughout ileum and colon. At this aim, Eudragit® S 100, a polymer soluble at pH > 7, commonly used for enteric release of drugs, has been successfully spun into ultrafine fibers loaded with Budesonide (B) at 9% and 20% (w/w) using the electrospinning process. The physico-chemical characterization by scanning electron microscopy, X-ray diffraction, FTIR spectroscopy, and thermal analyses indicated the amorphous nature of budesonide in the electrospun systems. Dissolution rate measurements using a pH-change method showed negligible drug dissolved at pH 1.0 and sustained release at pH 7.2. Therefore, the pharmaceutical systems proposed, made of fibers, represent an effective method for drug targeting to terminal ileum and colon with the aim of improving the local efficacy of this drug.

Polymorphic solidification of Linezolid confined in electrospun PCL fibers for controlled release in topical applications

Poly(ϵ-caprolactone) (PCL) membranes loaded with Linezolid, chemically N-[[(5S)-3-[3-fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide (empirical formula C16H20FN3O4) have been prepared by electrospinning technique, at different Linezolid concentrations (0.5, 1, 2.5 and 5%, w/w). Structural characterization, morphological analysis and the study of the mechanical properties have been performed on loaded membranes and compared with neat PCL membranes. Linezolid embedded in the membranes is prevalently amorphous, with a low crystallinity showing a different polymorphic form respect to the usual Form I and Form II. The release kinetics of the drug were studied by spectrophotometric analysis (UV-vis). It allowed to discriminate between Linezolid molecules on the surface and encapsulated into the fibers. The antibacterial activity of the electrospun membranes was effective to inhibit Staphylococcus aureus. The properties of the loaded membranes and their capability for local delivery of the antibiotic make them good candidates as drug release devices for topical use.

Hydrotalcites in nanobiocomposites

Abstract: This chapter deals with the preparative methods, structural aspects and chemical–physical characteristics of hydrotalcite-like compounds (HTlc), an emerging class of layered solids with anion exchange and intercalation properties. Biocompatible HTlc can be modified with molecular anions having pharmaceutical, antimicrobial or antioxidant activity to obtain materials that can release the active anions in different environments with a de-intercalation process. Moreover, the organic–inorganic hybrids can exfoliate when dispersed in polymeric matrices and act as active fillers of biocompatible and biodegradable polymers. The fillers could enhance the mechanical and barrier properties of the polymer and confer on it biological activity for application in food packaging, particularly in active packaging technologies and in biomedical devices.

Fabrication and characterization of electrospun polylactide/β-tricalcium phosphate hybrid meshes for potential applications in hard tissue repair

Abstract Non-woven hybrid meshes based on poly(l-lactide-co-d,l-lactide) (dl-PLA) and β-tricalcium phosphate (β-TCP) were fabricated and comprehensively characterized. Stock suspensions of β-TCP powder in dl-PLA acetone solutions were used for the electrospinning process. Structure, morphology and thermal properties of the electrospun samples were investigated by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The electrospun hybrid materials show a micro-composite structure, and a morphology characterized by a three-dimensional porous fibrous mesh with randomly distributed fibers possessing average fiber diameters between 680 and 970 nm, uniform thickness along the fibers and beads structure only for higher β-TCP concentration electrospun samples. Both pure PLA and hybrid non-woven meshes exhibit a good thermal stability and a continuous degradation in simulated body fluid medium. A live/dead staining viability assay using MC3T3-E1 preosteoblasts reveals the excellent cytocompatibility of the fabricated non-wovens. Enhanced alkaline phosphatase (AP) activity of MC3T3-E1 cells during culture on the dl-PLA and the composite non-woven meshes demonstrates their potential for applications in hard tissue repair.