Biomedical subjects

Y H Bae

Publications and source records attributed to Y H Bae.

35 records · Page 2Linked to original sources

PubMed1998

Extracellular matrix for a rechargeable cell delivery system.

Above a critical concentration, aqueous polymer solutions of N-isopropylacrylamide copolymers with small amounts of acrylic acid, synthesized in benzene by radical polymerization, exhibited four distinct phases as the temperature increased; clear solution, opaque solution, gel and shrunken gel. The transition between the opaque solution phase and the gel phase was in the range of 30-34 degrees C and was reversible without syneresis and noticeable hysteresis under the experimental conditions used in this study. Islets of Langerhans, isolated from Sprague-Dawley rat pancreata and entrapped in the gel matrix, remained viable, with no significant decrease in insulin secretion function in vitro for one month. When islets were encapsulated with the gel matrix in hollow fibers [molecular weight cut-off (MWCO)= approximately 400000] and were exposed to dynamic changes in glucose and theophylline concentrations, their insulin secretion patterns demonstrated a smaller lag time and higher amplitude in insulin release than islets entrapped in a conventional alginate matrix under the same experimental conditions. From these two observations, i.e. gel reversibility and islet functionality in the matrix observed in in vitro experiments, the N-isopropylacrylamide copolymers with acrylic acid synthesized in this study are optimum candidates for the extracellular matrix in a diffusion chamber-type cell delivery system in order to recharge the entrapped cells when cell functionality in the system decreases.

Acrylamides↗

PubMed1998

Synthesis of sulfonylurea conjugated copolymer via PEO spacer and its in vitro short-term bioactivity in insulin secretion from islets of Langerhans.

In order to reduce the number of immunoprotected islets required in xeno- or allogenic transplants for reversing diabetes, analogues of glyburide (a sulfonylurea), an extremely hydrophobic insulin secretagogue, were synthesized and used in an attempt to produce water soluble sulfonylurea (SU) grafted polymers. After synthesizing various polymers containing glyburide analogues, a poly(N-vinyl-2-pyrrolidone-co-sulfonylurea succinyl PEO (Mw = 3000) acrylate) was found to be soluble in a cell culture medium at pH 7.4. However, solubility was only obtained by decreasing solution pH from 11 to 7.4. When the copolymer was added to the islet cell culture media at a concentration of 5 microg ml(-1) (based on the theoretical SU content of the copolymer), insulin secretion was enhanced by about 30% at low glucose concentrations of 50 and 100 mg dl(-1) compared to the control. This is equivalent to 40-60% bioactivity of glyburide. The polymer's effect on insulin secretion at a higher glucose concentration of 200 mg dl(-1) was not significant. Considering the previous results where a similar but insoluble polymer without a PEO spacer was used and the polymer showed SU bioactivity only at a glucose concentration of 50 mg dl(-1), the observations from this study indicates that the solubility of SU-grafted polymers may affect the binding of SU groups to SU receptors on the pancreatic beta-cells, resulting in improved pharmacodynamic effect of SU.

ATP-Binding Cassette Transporters↗

PubMed1997

Biodegradable block copolymers as injectable drug-delivery systems.

Polymers that display a physicochemical response to stimuli are widely explored as potential drug-delivery systems. Stimuli studied to date include chemical substances and changes in temperature, pH and electric field. Homopolymers or copolymers of N-isopropylacrylamide and poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (known as poloxamers) are typical examples of thermosensitive polymers, but their use in drug delivery is problematic because they are toxic and non-biodegradable. Biodegradable polymers used for drug delivery to date have mostly been in the form of injectable microspheres or implant systems, which require complicated fabrication processes using organic solvents. Such systems have the disadvantage that the use of organic solvents can cause denaturation when protein drugs are to be encapsulated. Furthermore, the solid form requires surgical insertion, which often results in tissue irritation and damage. Here we report the synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid). Aqueous solutions of these copolymers exhibit temperature-dependent reversible gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45 degrees C), where they form a sol. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained-release matrix for drugs.

Animals↗

PubMed1997

Pure or predominant sensory stroke due to brain stem lesion.

BACKGROUND AND PURPOSE: Pure or predominant hemisensory symptoms can be seen in patients with brain stem stroke. However, there have been no reports in which sufficient numbers of patients were studied with detailed descriptions on the sensory patterns and imaging findings. METHODS: We describe 17 patients presenting with pure or predominant hemisensory symptoms due to brain stem stroke in whom CT scan and/or MRI identified appropriate lesions. RESULTS: Eleven patients had an infarct and 6 had a hemorrhage. Aside from sensory deficit, the majority had dizziness and gait ataxia. Fifteen patients had paramedian dorsal pontine lesions associated with pure or predominant lemniscal sensory involvement, often in the cheiro-oral (n = 4) or leg dominance (n = 4) patterns. The lesions of the former group tended to be located more medially compared with those of other patients, which is in agreement with the sensory topography of the pontine lemniscal sensory tract. Bilateral facial or perioral sensory symptoms were noted in 6 patients. One patient with a dorsolateral pontine lesion had selective spinothalamic modality impairment, while one with a lateral midbrain infarct had sensory deficit of all modalities. CONCLUSIONS: Pure or predominant brain stem sensory stroke is most often produced by small infarcts or hemorrhages in the paramedian dorsal pontine area and may be differentiated from thalamic pure sensory stroke by the following characteristics: frequent association of dizziness/gait ataxia, predominant lemniscal sensory symptoms, occasional leg dominance or cheiro-oral pattern, and frequent bilateral perioral involvement.

Aged↗

PubMed1995

Heparin release from thermosensitive polymer coatings: in vivo studies.

Biomer/poly(N-isopropylacrylamide)/[poly(NiPAAm)] thermosensitive polymer blends were prepared and their application as heparin-releasing polymer coatings for the prevention of surface-induced thrombosis was examined. The advantage of using poly (NiPAAm)-based coatings as heparin-releasing polymers is based on the unique temperature-dependent swelling of these materials. At room temperature, i.e., below the lower critical solution temperature (LCST) of poly (NiPAAm), the Biomer/(poly(NiPAAm) coatings are highly swollen. The high swelling enables fast loading of hydrophilic macromolecules (e.g., heparin) into the coating by a solution sorption technique. At a body temperature, i.e., above the LCST of poly (NiPAAm) the coatings are in a deswollen state and the absorbed macromolecules may be slowly released from a dense coating via a diffusion controlled mechanism. Biomer/poly(NiPAAm) coatings were obtained by blending and coprecipitation of the two linear polymers, Biomer and (poly(NiPAAm). The structure and water-swelling properties of the coatings were examined. Significant differences in water swelling at room temperature (RT) and 37 degrees C were observed as a result of the thermosensitivity of poly (NiPAAm). The surface structure of the coatings in dry and swollen states at RT and 37 degrees C was examined by scanning electron microscopy. Heparin was loaded into the coatings via a solution sorption at room temperature. Kinetic studies of heparin loading demonstrated that maximum loading was obtained within 1 h. The in vitro (37 degrees C) release profiles were characterized by a rapid initial release due to the squeezing effect of the collapsing polymer network, followed by a slower release phase controlled by heparin diffusion through the dense coating. The short-term antithrombogenicity of intravenous polyurethane catheters coated with heparin-releasing Biomer/poly(NiPAAm) thermosensitive coating was evaluated in a canine animal model. The results show that the heparin release from Biomer/poly(NiPAAm)-coated surfaces resulted in a significant reduction of thrombus formation on test surfaces in contact with venous blood as compared to control surfaces.

Acrylic Resins↗

PubMed1994

Preparation and characterization of albumin-heparin microspheres.

Albumin-heparin microspheres were prepared by a two-step process which involved the preparation of a soluble albumin-heparin conjugate, followed by formation of microspheres from this conjugate or by a double cross-linking technique involving both coupling of soluble albumin and heparin and microsphere stabilization in one step. The first technique was superior since it allowed better control over the composition and the homogeneity of the microspheres. Microspheres could be prepared with a diameter of 5-35 microns. The size could be controlled by adjusting the emulsification conditions. The degree of swelling of the microspheres was sensitive to external stimuli, and increased with increasing pH and decreasing ionic strength of the medium.

Albumins↗

PubMed1994

Degradation and intrahepatic compatibility of albumin-heparin conjugate microspheres.

The in vitro degradation properties of glutaraldehyde cross-linked albumin and albumin-heparin conjugate microspheres (AMS and AHCMS respectively) were evaluated using light microscopy, turbidity measurements and heparin release determinations, showing that the microspheres are degraded by proteolytic enzymes such as trypsin, proteinase K and lysosomal enzymes. The degradation rate was inversely related to the cross-link density of the microspheres. After intrahepatic administration of AHCMS, cross-linked with 0.5% glutaraldehyde, to male Wag/Rij rats by injection into a mesenteric vein (intravenoportal: i.v.p.), the microspheres were entrapped in the hepatic vascular system. The AHCMS were entrapped within terminal portal veins predominantly at the periphery of the liver. The AHCMS were degraded by cellular enzymatic processes within 2 wk after injection, with a half life of approximately 1 d. Biocompatibility of AHCMS and adriamycin-loaded AHCMS was evaluated by histological assessment of the mitotic activity of liver parenchyma and inflammatory response, and by determination of liver damage marker enzymes during 4 wk after administration. Liver damage marker enzymes were not increased compared with controls, nor were adverse effects observed upon histological examination. There was no difference in response between empty and adriamycin-loaded AHCMS.

Albumins↗

PubMed1992

Concanavalin A microspheres for a self-regulating insulin delivery system.

A self-regulating insulin delivery system based on the competitive binding of glucose and p-succinylamidophenyl-alpha-D-glycopyranoside-insulin (SAPG-insulin) to crosslinked concanavalin A (Con A) microspheres (MSs) has been investigated. Con A MSs prepared by a water-in-oil emulsion technique demonstrated properties of binding to glucose and SAPG-insulin (binding constants of 1.25 x 10(3) and 1.28 x 10(4) M-1, respectively) that are similar to the literature values of these properties for unmodified Con A. The retained binding capacity (number of binding sites per molecule) of Con A MSs, produced with 20% of the epsilon-amino groups crosslinked, was approximately 28% that of intact Con A. As a new device, Con A MSs loaded with SAPG-insulin was enclosed in a heat-sealed, surface-modified, porous poly(vinylidene difluoride) membrane pouch. This system showed a pulsatile release pattern for insulin with a short lag time in response to glucose challenges of 50-500 mg/dL. The pattern of release of SAPG-insulin from the devices was studied with varying design parameters, such as surface area, membrane pore size, and loading content of SAPG-insulin.

Binding, Competitive↗

PubMed1992

Hydrogels: swelling, drug loading, and release.

Hydrogels have been used by many investigators in controlled-release drug delivery systems because of their good tissue compatibility and easy manipulation of swelling level and, thereby, solute permeability. The desired kinetics, duration, and rate of solute release from hydrogels are limited to specific conditions, such as hydrogel properties, amount of incorporated drug, drug solubility, and drug-polymer interactions. This review summarizes the compositional and structural effects of polymers on swelling, loading, and release and approaches to characterize solute release behavior in a dynamic state. A new approach is introduced to compensate drug effects (solubility and loading) with the release kinetics by varying the structure of heterogeneous polymers. Modulated or pulsatile drug delivery using functional hydrogels is a recent trend in hydrogel drug delivery.

Drug Carriers↗

PubMed1991

Electrically erodible polymer gel for controlled release of drugs.

New controlled drug-delivery systems are being explored to overcome the disadvantages of conventional dosage forms. For example, stimulated drug-delivery has been used to overcome the tolerance problems that occur with a constant delivery rate, to mimic the physiological pattern of hormonal concentration and to supply drugs on demand. Stimuli-sensitive polymers, which are potentially useful for pulsed drug delivery, experience changes in either their structure or their chemical properties in response to changes in environmental conditions. Environmental stimuli include temperature, pH, light (ultraviolet or visible), electric field or certain chemicals. Volume changes of stimuli-sensitive gel networks are particularly responsive to external stimuli, but swelling is slow to occur. As well as being useful in the controlled release of drugs, such systems also provide insight into intermolecular interactions. Here we report on a novel polymeric system, which rapidly changes from a solid state to solution in response to small electric currents, by disintegration of the solid polymer complex into two water-soluble polymers. We show that the modulated release of insulin, and by extension other macromolecules, can be achieved with this polymeric system.

Acrylic Resins↗

PubMed1991

"On-off" thermocontrol of solute transport. II. Solute release from thermosensitive hydrogels.

Poly(N-isopropylacrylamide) (NIPAAm)/polytetramethylene ether glycol (PTMEG) interpenetrating polymer networks (IPNs) were synthesized and their feasibility as thermosensitive hydrogels for drug release was investigated. The release of indomethacin incorporated into these matrices showed pulsatile patterns in response to temperature changes and was sensitive to a few degrees of temperature fluctuation. The temperature inducing on-off release deviated from the gel collapse temperature of unloaded gel, possibly because of solute effects on network properties. The lag time and release profile of indomethacin in the low-temperature region (on process) of each temperature cycle were affected by the gel composition and applied temperature. The results of this study demonstrate that solute release can be regulated by rapid deswelling of the surface of the gels in response to temperature.

Drug Carriers↗

PubMed1991

"On-off" thermocontrol of solute transport. I. Temperature dependence of swelling of N-isopropylacrylamide networks modified with hydrophobic components in water.

The swelling in water, as a function of temperature, of two series of N-isopropylacrylamide (NIPAAm) polymer networks was studied. In the first series, n-butylmethacrylate (BMA) was copolymerized with NIPAAm, and in the second, polytetramethylene ether glycol (PTMEG) was incorporated into NIPAAm network as a chemically independent interpenetrating network. With increasing BMA content in the poly(NIPAAm-co-BMA) network, the gel collapse point was lowered and the gels deswelled in a more gradual manner with increasing temperature. In the interpenetrating polymer networks (IPN) system, the gel collapse point was not significantly changed by the amount of incorporated PTMEG. In DSC thermograms of swollen samples, the shape and onset temperature of the endothermic peak corresponded to the gel deswelling behavior and gel collapse point. The temperature dependence of equilibrium swelling in water was shown to be a function of the gel composition in both network series. The synthesized networks formed a dense surface layer as the temperature increased past the gel collapse point. This dense layer retarded water efflux and thereby resulted in water pockets at the membrane surface.

Acrylamides↗

PubMed1991

Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: I. Drug release.

Thermosensitive co-polymers of isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA) are capable of 'on-off' regulation of drug release in response to external temperature changes due to skin formation with increasing temperature. To clarify the role of the surface-modulated skin and controlled pulsatile drug release patterns, the surface shrinking process was regulated by changing the length of the methacrylate alkyl side-chain. Release of indomethacin in response to stepwise temperature changes between 20 and 30 degrees C from co-polymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA) was studied. The drug release rate during the 'on' state (20 degrees C) remained constant before and after the 'off' state (30 degrees C) when the period of the 'off' state was increased. These results suggest that the drug in the polymeric matrices diffused from the inside to the surface during the 'off' state even when no drug release was seen. The length of alkyl side-chain was found to be an important parameter in controlling the thickness and density of the surface skin layer.

Cross-Linking Reagents↗

PubMed1972