Drug release from xyloglucan beads coated with Eudragit for oral drug delivery.

Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-%) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 +/- 30 to 819 +/- 50 microm were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.

Alginate microcapsules prepared with xyloglucan as a synthetic extracellular matrix for hepatocyte attachment.

In this study, xyloglucan (XG) was used as a new synthetic extracellular matrix (ECM) for primary mouse hepatocyte attachment in Ca-alginate (AL) capsules. The rates of hepatocytes adhesion onto collagen type I-, XG-coated and uncoated polystyrene (PS) surface were 89.1%, 91.1% and 25.5%, respectively, at 4 h after incubation at 37 degrees C. From the inhibition study in a cell adhesion assay, the adhesion rates of freshly isolated hepatocytes and preincubated hepatocytes with 20 mm galactose onto the XG-coated surface were 55.7 and 17.3%, respectively, after 30 min incubation at 37 degrees C. Flow cytometric analysis showed that the internalization of XG by freshly isolated hepatocytes was stronger than preincubated hepatocytes with 20 mm galactose. The concentration of XG in AL/XG capsules to perform the best liver-specific functions was 0.5 mg/ml, where the highest albumin secretion rates were obtained. The albumin secretion, ammonia elimination rates and cell viability of hepatocytes were slowly decreased with culture time in AL/XG capsules, whereas those were rapidly decreased in AL capsules, indication of the more rapid formation of hepatocyte spheroids in AL/XG capsules than in AL capsules. More than 70% of the seeded hepatocytes in AL/XG capsules participated in spheroid formation after 2 days, whereas most hepatocytes in AL capsules remained as single cells and only a few cells began to form aggregates after 3 days. Intercellular molecule genes, such as connexin (Cx) 32 and E-cadherin, of hepatocyte spheroids in AL or AL/XG capsules were detected by reverse transcriptase-polymerase chain reaction. Cx32 and E-cadherin genes in AL/XG capsules were more rapidly reexpressed and expressed, respectively, than in AL ones. The results suggest that the multicellular spheroid formation of hepatocytes can enhance the liver-specific functions in the three-dimensional space in the presence of XG as a new synthetic ECM owing to the specific interaction between the galactose moieties of XG and asialoglycoprotein receptors of hepatocytes.

Xyloglucan as a synthetic extracellular matrix for hepatocyte attachment.

The possibility of employing naturally derived xyloglucan (XG) having galactose moieties in the side chain for the development of synthetic extracellular matrix in tissue engineering was studied. Hepatocyte adhesion to the XG-coated polystyrene (PS) dish was 73.9% after 30 min incubation, whereas that to the PS dish as a negative control was 59.1%. The hepatocyte adhesion to the XG-coated surface was dependent on the presence of Ca2+ ions, whereas that to the XG-coated surface could not be induced by Mg2+ ions alone, indicating specific interaction between galactose moieties of XG and asialoglycoprotein receptors of hepatocytes. From the results of fluorescence, confocal laser micrographs and flow cytometry, it was suggested that XG was internalized by hepatocytes through a receptor-mediated mechanism. The DNA synthesis of hepatocytes attached to the XG-coated surface was decreased with an increase of the coating concentration of XG and in the presence of epidermal growth factor (EGF). The spreading shapes of the hepatocytes attached to the surface in the presence of EGF at low concentration of XG (1 microg/ml) were enhanced. The hepatocytes attached to the surface at a high concentration of XG (200 microg/ml) showed round shapes with spheroids after 16 h in the presence of EGF.

Synergistic gel formation of xyloglucan/gellan mixtures as sudied by rheology, DSC, and circular dichroism.

The gelation behavior of mixtures of tamarind seed xyloglucan (TSX) and sodium form gellan (Na-G) was investigated. The storage and loss shear moduli, G' and G'', of the mixtures showed that a thermoreversible gel was obtained although each polysaccharide alone did not form a gel at experimental conditions. The viscoelastic behavior of the mixtures showed a gel formation of TSX and Na-G induced by synergistic interaction. This synergistic interaction was also revealed by differential scanning calorimetry (DSC) and circular dichroism. Although TSX alone did not show any peak in DSC curves, mixtures with only a small amount of Na-G, which by itself did not show any peak, showed a single peak. With increasing Na-G content, another peak began to appear at the same temperature at which a peak of Na-G alone appeared. Thermally induced changes in circular dichroism of the mixtures were different from those expected from the individual behavior of TSX and Na-G.