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Biomedical subjects

You Han Bae

Publications and source records attributed to You Han Bae.

45 records · Page 3Linked to original sources

Assessment of PEO/PTMO multiblock copolymer/segmented polyurethane blends as coating materials for urinary catheters: in vitro bacterial adhesion and encrustation behavior.

The effective long-term use of indwelling urinary catheters has often been hindered by catheter-associated infection and encrustation. In this study, the suitability of poly(ethylene oxide) (PEO)-based multiblock copolymer/segmented polyurethane (SPU) blends as coating materials for the commercial urinary catheters was assessed by measuring swellability, bacterial adhesion, and encrustation behavior. When exposed to PBS (pH 7.4), the blends absorbed a significant amount of water, which was proportional to the copolymer content. It was demonstrated from bacterial adhesion tests that compared to bare SPU, the blend surfaces could significantly reduce the adhesion of E. coli, P. mirabilis, and S. epidermidis; the number of adherent bacteria correlated with the amount of copolymer additive. indicating that the swellability of the blends affected bacterial adhesion. Of the bacteria studied, the greatest effect of the copolymer additive was observed in S. epidermidis adhesion, in which there was an 85% decrease compared to bare SPU with a small amount of copolymer additive as low as 5% based on a dried blend. By using an artificial bladder model, allowing the catheter to be blocked by encrustation, it was revealed that the blend surfaces could effectively resist encrustation. The duration of patency was extended up to 20 +/- 3.1 h on the blend surface containing 10% of the copolymer additive, whereas the silicone-coated catheter, a control, required the least time for blockage, 7.8 +/- 3.1 h. The superior characteristics of the blends compared to other surfaces might be attributed to their PEO-rich surfaces, produced by the migration of PEO phase in the copolymer chain of the blends in an aqueous environment, and provide promising potential as a coating material on the urinary catheter for long-term catheterization.

Bacterial Adhesion↗

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↗

Effect of cross-linked hemoglobin on functionality and viability of microencapsulated pancreatic islets.

Of many obstacles involved in developing a bioartificial pancreas, which consists of encapsulated and physically immunoprotected islets, for long-term implantation in insulin-dependent diabetic patients, the impaired functionality and decreasing viability of encapsulated islets over time are critical factors in determining the size and longevity of the implant. These factors are closely associated with short oxygen supply to the encaged islets from the implant site. To facilitate oxygen transport to islets in the capsules, we coencapsulated hemoglobin cross-linked with difunctional polyethylene glycol (Hb-conjugate, Hb-C) which is large in size (>100 kDa), thus preventing diffusional loss through the immunoprotecting membrane. The coencapsulation of Hb-C with islets in alginate-poly-L-lysine microcapsules by dissolving Hb-C in an islet-suspended alginate solution at a concentration of 0.25 mM improved the insulin secretion and viability of the islets. At week 0, the islets, coencapsulated with Hb-C, cultured at P(O2) = 40 mmHg (assumed oxygen partial pressure in the most common implant site, the peritoneal cavity), secreted 200% more insulin compared with the control islets without Hb-C at glucose concentrations of both 100 and 300 mg/dL. The Hb-C effect became more significant with time at higher glucose concentrations. After culturing the islets for 8 weeks at 40 mmHg, the insulin secretion was enhanced 200 and 550% at glucose concentrations of 100 and 300 mg/dL as compared with the control, respectively. The results were closely associated with improved viability and suggest that the introduction of Hb-C is an effective approach to maintaining the oxygen supply to encapsulated islets. In addition, Hb-C coencapsulation with pancreatic islets may (1) provide a partial clue to reducing the large size of the biohybrid artificial pancreas, (2) lead to a reduced need for pancreas donation, and (3) prolong the longevity of the biohybrid artificial pancreas in the body.

Animals↗

Physicochemical properties and in vitro biocompatibility of PEO/PTMO multiblock copolymer/segmented polyurethane blends.

A multiblock copolymer composed of poly(ethylene oxide) (PEO) and poly(tetramethylene oxide) (PTMO) and which forms a physical hydrogel was blended with Pellethane, a commercial segmented polyurethane (SPU) developed for various biomedical devices, to provide a PEO-rich surface with improved stability. The effect of the copolymer blending was evaluated with respect to surface hydrophilicity, long-term stability, mechanical properties, in vitro protein adsorption, and platelet adhesion. A small amount of the copolymer additive (5 wt%) significantly improved surface hydrophilicity, which was then gradually enhanced by increasing the amount of the copolymer in the blends. The blend films exhibited minimal extraction of the copolymer additive when exposed to a buffer solution for 2 months at 37 degrees C, resulting in less than 1 wt% weight loss of the films even with 30 wt% content of the copolymer in the blends. Although a certain degree of alteration in the mechanical properties was observed by increasing the copolymer content, the mechanical properties were well maintained for up to 10 wt% addition of the copolymer, when compared with the bare SPU. Protein adsorption was significantly reduced with a small amount of copolymer additive as low as 5 wt%. Fibrinogen, an adhesive protein for further cellular adhesion and activation, was effectively repelled by increasing the amount of copolymer additive. The platelet adhesion test revealed that the blend film surface reduced platelet adhesion and the degree of inhibition was proportional to the content of the additive, up to 30 wt%. The high molecular weight (Mw = 66,000) and compatible chemical structure of the copolymer with SPU made the surfaces PEO-rich and stable in an aqueous environment, resulting in an enhancement of the resistance to protein adsorption and platelet adhesion without a significant deterioration in physical properties.

Adsorption↗

Phenotype of hepatocyte spheroids in Arg-GLY-Asp (RGD) containing a thermo-reversible extracellular matrix.

The spheroid of specific cells is often regarded as the better form in artificial organs and mammalian cell bioreactors for improved cell-specific functions. In this study, freshly harvested primary rat hepatocytes, which had been cultivated as spheroids and entrapped in a synthetic thermo-reversible extracellular matrix, were examined for differentiated morphology and enhanced liver-specific functions as compared to a control set (hepatocytes in single-cell form). A copolymer of N-isopropylacrylamide (98 mole % in the feed) and acrylic acid (poly(NiPAAm-co-AAc)), and the adhesion molecule, an Arg-Gly-Asp (RGD)-incorporated thermo-reversible matrix, were used to entrap hepatocytes in the form of either spheroids or single cells. In a 28-day culture period, the spheroids in the RGD-incorporated gel maintained higher viability and produced albumin and urea at constant rates, while there was lower cell viability and less albumin secretion by the spheroids in p(NiPAAm-co-AAc). Hepatocytes cultured as spheroids in the RGD-incorporated gel would constitute a potentially useful three-dimensional cell system for application in a bio-artificial liver device.

Acrylic Resins↗

Visual evidence and quantification of interaction of polymeric sulfonylurea with pancreatic islet.

Using a polymeric sulfonylurea (PSU) designed from glibenclamide, we examined the interactions of sulfonylurea with pancreatic islets rather than genetically remodeled beta-cell lines to clarify the biological roles of ATP-sensitive K+ (KATP) channels to which sulfonylurea binds. PSU enhanced insulin secretion from the islets with 10 nM (SU equivalent) treatment, especially at low glucose concentration, but its activity was inhibited by 100 microM diazoxide. Confocal microscopy visualized PSU interactions with the islet and revealed that the modulation of intracellular Ca2+ occurred in the same region of an islet where PSU was also bound. In quantification method of the confocal microscopic images, competition of PSU with glibenclamide on its binding sites and glucose inhibition against PSU binding were confirmed. In this study, it was concluded that the PSU was a comparable drug with glibenclamide and offered a new standard method to study intact islets.

Animals↗

Caprolactonic poloxamer analog: PEG-PCL-PEG.

The aqueous solution of poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymers (> 15. wt. %) undergoing "clear sol-gel-turbid sol" transition as the temperature increases from 20 to 60 degrees C has been developed. Light scattering and 13C NMR study suggested that the transition mechanisms are the micellar aggregation for the clear sol to gel transition (lower transition), whereas the increase in PCL molecular motion for gel to turbid sol transition (upper transition). In contrast to the previous thermogelling biodegradable polymers with a sticky paste morphology, the powder form of the PEG-PCL-PEG triblock copolymers makes it easy to handle and allows fast dissolution in water. Therefore, the lyophilization into a powder form followed by facile reconstitution was possible. This system is believed to be promising for drug delivery, cell therapy, and tissue engineering.

Biocompatible Materials↗

Novel injectable pH and temperature sensitive block copolymer hydrogel.

A novel pH and temperature sensitive block copolymer was prepared by adding pH sensitive moiety to temperature sensitive block copolymer. This block copolymer solution showed a reversible sol-gel transition by a small pH change in the range of pH 7.4-8.0 and also by the temperature change in the region of body temperature. The very precise molecular weight control of block copolymer and the prudential tuning of hydrophilic-hydrophobic balance were needed to control the phase diagram. This block copolymer solution forms a gel at 37 degrees C, pH 7.4 (human body). When the block copolymer solution is at room temperature and pH 8.0 as a sol state, both the temperature and pH change are needed for the gelation. This material can be employed as injectable carriers for hydrophobic drugs and proteins, etc. Gelation inside the needle can be prevented by an increase in the temperature during injection, because it does not change into the gel form with only increasing temperature. This material can be used for even a long guide catheter into the body. The block copolymer hydrogel which shows the sol-gel transition by the small pH change from pH 8.0 to pH 7.4 has merits in the delivery system for protein and cells which show cytotoxicity in acidic (below pH 6.5) or basic (above pH 8.5) conditions. This block copolymer system could be used as a template technology for injectable delivery systems.

Biocompatible Materials↗

Long-term insulinotropic activity of glucagon-like peptide-1/polymer conjugate on islet microcapsules.

The biohybrid artificial pancreas (BAP), a promising therapy for type 1 diabetes, faces several obstacles such as the need for a large implantation volume of encapsulated islets because of low functionality. To address such problems, in this study we examined long-term insulinotropic activity of glucagon-like peptide-1 (GLP-1)/polymer conjugate [VAPG: poly(N-vinylpyrrolidone-co-acrylic acid-g-PEG) (VAP)-GLP-1] as well as GLP-1/Zn(2+) crystal by coencapsulation with islets. Microcapsules with VAPG or crystal produced round-shaped beads whereas free GLP-1 showed poor capsule morphology. A perfusion experiment suggested that VAPG showed higher bioactivity than did microcapsules with GLP-1/Zn(2+). In long-term culture (200 mg of glucose/dL [G]), VAPG also enhanced insulinotropic activity over 5 weeks compared with the crystal form of GLP-1. However, maintenance of the high bioactivity of VAPG suddenly declined after week 5, possibly because of degradation, metabolism, and overstimulation. Basal (50 G) and glucose-stimulated (300 G) levels of insulin secretion confirmed a see-saw pattern in which the VAPG gradually decreased insulin secretion from encapsulated islets and then fell below the insulin level secreted from microcapsules containing GLP-1/Zn(2+) crystal. Viability of the microcapsulated islets of each group was not significantly different. Consequently, the coencapsulation of VAPG or GLP-1/Zn(2+) crystal can be a potential approach to reducing BAP volume with further optimization of activity duration.

Animals↗