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Biomedical subjects

Kun Na

Publications and source records attributed to Kun Na.

23 records · Page 2Linked to original sources

Insulinotropic activity of sulfonylurea/pullulan conjugate in rat islet microcapsule.

The in vitro long-term effect of a water-soluble sulfonylurea/pullulan conjugate (SUP) on insulinotropic activity and cell viability was investigated using rat pancreatic islets co-entrapped with SUP in conventional alginate-poly(L-lysine) microcapsules. The conjugate was synthesized by coupling a carboxylated glibenclamide derivative to a polysaccharide, pullulan (MW=200,000). In vitro static experiment showed that sulfonylurea concentration in SUP over 50 microM was required to stimulate the rat islets. In a dynamic insulin secretion test, the microcapsules of islets with SUP regained the insulin secretion pattern comparable to that of free islets, while those without SUP showed impaired insulin secretion. The long-term (1 month) culture experiment demonstrated that the microcapsules of islets with SUP, with well-preserved morphology, presented higher insulin secretion level and better ability in responding to glucose changes than those without SUP.

Alginates↗

Self-assembled nanoparticles of hydrophobically-modified polysaccharide bearing vitamin H as a targeted anti-cancer drug delivery system.

Vitamin H (biotin) was incorporated into a hydrophobically modified polysaccharide, pullulan acetate (PA), in order to improve the cancer-targeting activity and internalization of self-assembled nanoparticles. The biotinylated pullulan acetate (BPA) nanoparticles were prepared by a diafiltration method and the mean diameter was approximately 100 nm. Three samples of biotinylated pullulan acetate (BPA), comprising 7 (BPA 1), 20 (BPA 2), and 39 (BPA 3) vitamin H groups per 100 anhydroglucose units of PA, were synthesized. The critical aggregation concentrations (CAC) of the BPA nanoparticles in distilled water were 3.1 x 10(-3), 4.3 x 10(-3) and 6.8 x 10(-3) mg/ml for BPA 1, BPA 2, and BPA 3, respectively. Adriamycin (ADR) was loaded into the BPA nanoparticles as a model drug. The loading efficiencies and ADR content in the BPA nanoparticles decreased with increasing vitamin H content due to a lower hydrophobicity. The RITC-labeled BPA nanoparticles exhibited very strong adsorption to the HepG2 cells, while the RITC-labeled PA nanoparticles did not show any significant interaction. The degree of the interaction increased with increasing vitamin H content. Confocal laser microscopy also revealed that internalization of the BPA nanoparticles into the cancer cells depended on the vitamin H content.

Antineoplastic Agents↗

Conjugation of heparin into carboxylated pullulan derivatives as an extracellular matrix for endothelial cell culture.

A carboxylated pullulan, for use as a structural material for a number of tissue engineering applications, was synthesized and conjugated with heparin. By immobilization of heparin to pullulan, endothelial cells (ECs) attached on the heparin-conjugated pullulan were more aggregated than when attached to other pullulan derivatives. Attachments were 50, 45, 49, and 90% for a polystyrene dish, pullulan acetate, carboxylated pullulan, and heparin-conjugated pullulan, respectively. Heparin-conjugated pullulan inhibited the proliferation of smooth muscle cells (SMCs) in vitro. Heparin-conjugated pullulan material can thus be used for the proliferation of vascular ECs and to inhibit the proliferation of SMCs.

Animals↗

Probe of specific interaction between a simplified synthetic glycopolymer and erythrocytes as mediated by a glucose transporter (GLUT) on a cell membrane.

In order to develop a biomimetic polymer for cell recognition, we synthesized poly [3-O-(4'-vinylbenzyl)-D-glucose] (PVG), a polystyrene derivative with reduced glucose moiety, and studied the specific interaction of this PVG with erythrocytes, carried by a glucose transporter (GLUT-1), on a cell membrane. To clarify the specific interaction between the PVG and the erythrocytes, fluorescein isothiocyanate- (FITC) labeled polymer was used to prove and visualize the specific interaction. We found that labeled polymer strongly binds to erythrocytes, probably due to the specific interaction mediated by the presence of GLUT-1 on the cell membrane. The fluorescence intensity of PVG on erythrocytes was time and dose dependent. To verify the specific interaction between the PVG and the erythrocytes, cells were pretreated with phloretin, an inhibitor of GLUT-1, before adding the FITC-labeled PVG polymer to the cell-culture medium. This treatment suppressed the interaction of PVG with erythrocytes. A confocal laser microscopic study further confirmed this interaction. The results from this study provide evidence that a biomimetic polymer of PVG interacts with erythrocytes mediated by GLUT-1 on cell membranes.

Dose-Response Relationship, Drug↗

Self-assembled hydrogel nanoparticles responsive to tumor extracellular pH from pullulan derivative/sulfonamide conjugate: characterization, aggregation, and adriamycin release in vitro.

PURPOSE: To investigate some physicochemical properties of self-assembled hydrogel nanoparticles of pullulan acetate (PA) and sulfonamide conjugates, as a potential tumor targeting drug carrier responsive to tumor extracellular pH. METHODS: A new class of pH-responsive polymers was synthesized by conjugating a sulfonamide, sulfadimethoxine (SDM), to succinylated pullulan acetate (coohPA). The polymers formed self-assembled PA/SDM hydrogel nanoparticles in aqueous media, which was confirmed by fluorometry and field emission-scanning electron microscopy. The pH-dependent behavior of the nanoparticles was examined by measuring transmittance, particle size and zeta potential. Adriamycin (ADR) was tested for loading into and release from the nanoparticles at various pHs. RESULTS: The mean diameters of all PA/SDM nanoparticles tested were <70 nm. with a unimodal size distribution. The critical aggregation concentrations at pH 9.0 were as low as 3.16 microg/mL. The nanoparticles showed good stability at pH 7.4, but shrank and aggregated below pH 7.0. The ADR release rate from the PA/SDM nanoparticles was pH-dependent around physiological pH and significantly enhanced below a pH of 6.8. CONCLUSIONS: The pH-responsive PA/SDM nanoparticles may provide some advantages for targeted anti-cancer drug delivery due to the particle aggregation and enhanced drug release rates at tumor pH.

Antineoplastic Agents↗