Biomedical subjects

Tae Hee Kim

Publications and source records attributed to Tae Hee Kim.

12 recordsLinked to original sources

PubMed2006

Monodisperse hollow titania nanospheres prepared using a cationic colloidal template.

Titania-coated polymeric nanoparticles were synthesized based on the cationic colloidal particles which were prepared by surfactant-free emulsion copolymerization of styrene and butylacrylate in the presence of a cationic monomer, methacryloxyethyltrimethyl ammonium chloride (MOTAC) using azobis(isobutylamidine)hydrochloride (AIBA) as an initiator. These cationic particles were stabilized by poly(vinylpyrrolidone) (PVP). Then, these particles were dispersed in ethanol and mixed with titanium(IV) butoxide. Negatively charged titania precursors were rapidly hydrolyzed onto the cationic surfaces of colloidal particles. Subsequently, the samples were heated to 450 degrees C to form anatase TiO2 and to remove the colloidal template, which resulted in hollow nanospheres. The hollow titania particles were characterized with zeta analyzer, transmission electron microscopy, scanning electron microscopy, light scattering, X-ray diffraction, thermogravimetric analysis and FT-IR.

Journal Article↗

PubMed2006

Inhibition of nitric oxide synthase expression in activated microglia and peroxynitrite scavenging activity by Opuntia ficus indica var. saboten.

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO-), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. A butanol fraction obtained from 50% ethanol extracts of Opuntia ficus indica var. saboten (Cactaceae) stem (SK OFB901) and its hydrolysis product (SK OFB901H) inhibited the production of NO in LPS-activated microglia in a dose dependent manner (IC50 15.9, 4.2 microg/mL, respectively). They also suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells at higher than 30 microg/mL as observed by western blot analysis and RT-PCR experiment. They also inhibited the degradation of I-kappaB-alpha in activated microglia. Moreover, they showed strong activity of peroxynitrite scavenging in a cell free bioassay system. These results imply that Opuntia ficus indica may have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

Animals↗

PubMed2006

Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice.

The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.

Administration, Inhalation↗

PubMed2006

Mannosylated chitosan nanoparticle-based cytokine gene therapy suppressed cancer growth in BALB/c mice bearing CT-26 carcinoma cells.

Cancer immunotherapy relies on the ability of the immune system to destroy tumor cells selectively and to elicit a long-lasting memory of such activity. Interleukin-12 (IL-12) is an immunomodulatory cytokine produced primarily by antigen-presenting cells, which play an important role in promoting Th1-type immune response and cell-mediated immunity. To augment the antitumor immune action by in vivo IL-12 gene delivery, mannosylated chitosan (MC) was prepared to induce mannose receptor-mediated endocytosis of IL-12 gene directly into dendritic cells which reside within the tumor. Upon characterization, MC was proven to be suitable for IL-12 gene delivery due to good physicochemical properties and low cytotoxicity. In addition, MC exhibited much enhanced IL-12 gene transfer efficiency to dendritic cells rather than chitosan itself in terms of the induction of murine IL-12 p70 and murine IFN-gamma. In animal studies, intratumoral injection of MC/plasmid encoding murine IL-12 complex into BALB/c mice bearing CT-26 carcinoma cells clearly suppressed tumor growth and angiogenesis, and significantly induced cell cycle arrest and apoptosis. Therefore, this study provides a new MC-mediated cytokine gene delivery system for cancer immunotherapy.

Animals↗

PubMed2005

Synergistic effect of poly(ethylenimine) on the transfection efficiency of galactosylated chitosan/DNA complexes.

The use of chitosan for gene delivery is limited due to the low transfection efficiency and difficulty in transfecting into a variety of cell types, especially the hepatoma cells. In order to solve this problem, lactobionic acid (LA) bearing galactose group was coupled with water-soluble chitosan (WSC) for liver specificity and poly(ethylenimine) (PEI) was combined to galactosylated chitosan (GC)/DNA complexes to enhance the transfection efficiency. For initial study, the effect of PEI on the transfection efficiency of WSC/DNA complex was studied in HeLa, A549 and 293 T cells, and bafilomycin A1 was used to ascertain the mechanism of synergistic effect. Transfection efficiency, cytotoxicity, and physicochemical properties of GC/DNA complex combined with PEI were investigated to determine the potential for the hepatocyte-targeting. The combination of PEI with WSC/DNA and GC/DNA complex dramatically increased the luciferase expression 10- to 1000-fold in various cell lines, and the synergistic effect was proved to be induced by proton sponge effect of PEI. The transfection of GC/DNA complex in HepG2 was much higher than that of WSC/DNA even after combination with PEI, and was highly inhibited in the presence of galactose. Cytotoxicity of PEI was much decreased by combination with GC/DNA complex. And PEI was proved to be coated on the surface of GC/DNA complex through the ionic interaction.

Cell Line, Tumor↗

PubMed2005

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.

Administration, Oral↗

PubMed2004

Galactosylated chitosan/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier.

Water-soluble chitosan (WSC) was used to increase the stability of chitosan in water and decrease the cytotoxicity induced by acetic acid. Lactobionic acid (LA) bearing galactose group was coupled with WSC for hepatocytes specificity. The composition of galactose in galactosylated chitosan (GC) was determined by NMR spectroscopy. The GC was complexed with plasmid DNA in various GC/DNA (N/P) charge ratios and the resulting complex was characterized by dynamic light scattering, gel retardation, and turbidity to determine the particle sizes, complex formation, and complex stability, respectively. Cytotoxicity and transfection efficiency of GC were also studied in cultured HepG2 human hepatoblastoma cell line and HeLa human cervix epithelial carcinoma cells. The complete GC/DNA complex was formed at the charge ratio of 5 and the GC/DNA complex to DNase I resistance was obtained. Particle sizes decreased with increasing charge ratio of GC to DNA and had a minimum value around 120 nm at the charge ratio of 5. And no significant difference in particle sizes from the charge ratio of 5-20 was found. The suspension of GC/DNA complexes exhibited no significant change in turbidity at the charge ratios of 10, indicating the complete shielding of DNA charge. Cytotoxicity study showed that GC prepared by the water-soluble chitosan had no cytotoxic effects on cells. And transfection efficiency into HepG2, which has asialoglycoprotein receptors (ASGP-R), was higher than that into HeLa without ASGP-R.

Absorption↗

PubMed2004

A large pool of available folate exists in the large intestine of human infants and piglets.

Many microorganisms in the large intestine are capable of synthesizing folate. Preliminary evidence suggests that this folate may be absorbed. The purpose of the 2 experiments reported herein was to estimate the pool of folate in the feces of human infants and piglets and to ascertain, if absorbed, whether the quantity and form of folate are sufficient to potentially affect the folate status of the host organism. The folate content of milk fed to and of fecal solids collected from exclusively human milk-fed (n = 12) and formula-fed (n = 10) term infants (1-6 mo old) was determined microbiologically before (short-chain folates) and after folate conjugase (total folate) treatment. The folate content of formula fed and of feces collected from 10-d-old piglets (n = 10) was also determined microbiologically. The proportion of 5-methyltetrahydrofolate (5-methylTHF) in feces of human infants and piglets that was monoglutamylated was determined by HPLC analysis. The folate content of fecal solids collected from infants was 93.2 +/- 92.8 nmol/d (mean +/- SD), representing on average 50% (8.0-170.1%) of their mean estimated dietary folate intake. Fecal folate was largely present as short-chain folate (66 +/- 21.3%) with the predominant form being 5-methylTHF, 52.5 +/- 30.1% of which was monoglutamylated. In piglets, the folate content of feces was 301.3 +/- 145.7 nmol/d, representing 36% of their dietary folate intake. Piglet fecal folate was largely present as short-chain folate (68.1 +/- 12.6%) with the predominant species being 5-methylTHF, 29.3 +/- 33.2% of which was monoglutamylated. Collectively, these data suggest that the quantity and form of folate (monoglutamylated) in the large intestine of human infants and piglets are sufficiently large to potentially affect folate status.

Animals↗

PubMed2003

Efficient gene delivery by urocanic acid-modified chitosan.

Nonviral delivery systems for gene therapy have been increasingly proposed as safer alternatives to viral vectors. Chitosan is considered to be a good candidate for the gene delivery system since it is already known as a biocompatible, biodegradable, and low toxic material with high cationic charge potential. However, the use of chitosan for gene delivery is limited due to low transfection efficiency. To enhance the transfection efficiency, water-soluble chitosan (WSC) was coupled with urocanic acid (UA) bearing imidazole ring which can play the crucial role in endosomal rupture through proton sponge mechanism. The urocanic acid-modified chitosan (UAC) was complexed with DNA, and UAC/DNA complexes were characterized. The sizes of UAC/DNA complexes under physiological condition (109-342 nm) were almost same as those of chitosan-DNA complexes. UAC also showed good DNA binding ability, high protection of DNA from nuclease attack, and low cytotoxicity. The transfection efficiency of chitosan into 293T cells was much enhanced after coupling with UA and increased with an increase of UA contents in the UAC.

Cell Line↗

PubMed2003

Release of albumin from chitosan-coated pectin beads in vitro.

The release behavior of albumin from chitosan-coated pectin beads in vitro was investigated. The factors, such as concentration of CaCl(2), molecular weight of chitosan, pH of chitosan solution, and pH of release medium, which can have a significant effect on the release behavior from the beads, were discussed in this study. The loading efficiency (LE) of albumin showed maximum value when the concentration of CaCl(2) and the weight ratio of pectin to albumin were 2 wt.% and 2, respectively. The release of albumin from pectin beads could be retarded by coating with chitosan at various pH medium. The increase of the concentration of CaCl(2) induced the decrease of albumin release for uncoated-pectin beads, but not much difference of release for coated-pectin ones. The higher molecular weight of chitosan showed less albumin release than the lower one. The release of albumin from the chitosan-coated pectin beads was dependent on pH of coating solution and release medium, which might affect the degree of swelling of pectin beads.

Animals↗

PubMed2003

A novel degradable polycaprolactone networks for tissue engineering.

Polycaprolactone (PCL) macromer was obtained by the reaction of PCL diol with acryloyl chloride and confirmed using Fourier transform infrared and nuclear magnetic resonance spectrometer. Novel degradable PCL networks were prepared through photopolymerization of the PCL macromer. Thermal, mechanical, and morphological characteristics as well as degradability and biocompatibility of the PCL networks were investigated. Differential scanning calorimetry showed that the melting temperature and the calculated weight average crystallinity of PCL networks were decreased with a decrease of molecular weight of PCL diols due to the increased crosslinking density. Thermal stability of PCL networks was higher than that of PCL diols. PCL networks showed faster degradation, and higher compressive modulus and compressive recovery ratios than those of PCL itself because of their low crystallinity and the modification of terminal groups. The porosity of the PCL networks can be controlled by the amounts and size of porogen used. MG-63 osteoblast cell was attached and proliferated on PCL networks. PCL networks therefore may have considerable potential as scaffold for tissue engineering.

Biocompatible Materials↗

PubMedDate not supplied

Receptor-mediated gene delivery into antigen presenting cells using mannosylated chitosan/DNA nanoparticles.

Dendritic cells (DCs) are professional antigen presenting cells that induce, sustain, and regulate immune responses. Gene modification of DCs is of particular interest for immunotherapy of diseases where the immunes system has failed or is abnormally regulated, such as in cancer or autoimmune disease. Gene transfer using non-viral vectors is a promising approach for the safe delivery of therapeutic DNA. Among various non-viral vectors, chitosan is considered to be a good candidate for gene delivery system, however, lack of cell specificity and low transfection of chitosan need to be overcome prior to clinical use. In this study, mannosylated chitosan (MC) was prepared to induce the receptor-mediated endocytosis and targeting into antigen presenting cells (APCs), especially DCs having mannose receptors. MC showed great ability to form complexes with DNA and showed suitable physicochemical properties for gene delivery system. It had low cytotoxicity and exhibited much enhanced gene transfer efficiency on the macrophage cell line than chitosan itself. Also, MC/DNA complex was more efficient for transferring IL-12 gene into DCs rather than water-soluble chitosan (WSC)/DNA one, which resulted in better induction of INF-gamma from DCs. Therefore, MC is a promising gene delivery system for repeated administration to maintain sustained gene expression, thereby opening the possibility for immunotherapy.

Animals↗