• YAKHAK HOEJI
• /
• v.49 no.4
• /
• pp.268-274
• /
• 2005

Paclitaxel is an effective antineoplastic agent against ovarian, colon and breast tumors. But there have been many difficulties to formulate this drug due to the extremely low aqueous solubility. Paclitaxel is currently formulated in a vehicle composed of Cremophor EL and absolute ethanol mixture which is $5\~20$ fold diluted in normal saline or $5\%$ dextrose solution before I.V. injection. However, this formulation has many problems such as allergic reactions and drug precipitation on aqueous dilution. To overcome these problems, we prepared the micelle and microemulsion systems for parenteral administration of paclitaxel by using glycofurol, $Soluto^{(R)}lHS$ 15 and oleic acid. Phase diagram, pH-rate stability, particle size distributions and pharmacokinetics of the systems were studied. Micelles and microemulsions formulated as nano-particle delivery system were physically and chemically stable. Therefore, these formulations might be the promising alternative candidate for the parenteral delivery of paclitaxel.

• Korean Journal of Materials Research
• /
• v.20 no.3
• /
• pp.132-136
• /
• 2010

This study examined the biostability and drug delivery efficiency of g-$Fe_2O_3$ magnetic nanoparticles (GMNs) by cytotoxicity tests using various tumor cell lines and normal cell lines. The GMNs, approximately 20 nm in diameter, were prepared using a chemical coprecipitation technique, and coated with two surfactants to obtain a water-based product. The particle size of the GMNs loaded on hangamdan drugs (HGMNs) measured 20-50 nm in diameter. The characteristics of the particles were examined by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-TEM) and Raman spectrometer. The Raman spectrum of the GMNs showed three broad bands at 274, 612 and $771\;cm^1$. A 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed that the GMNs were non-toxic against human brain cancer cells (SH-SY5Y, T98), human cervical cancer cells (Hela, Siha), human liver cancer cells (HepG2), breast cancer cells (MCF-7), colon cancer cells (CaCO2), human neural stem cells (F3), adult mencenchymal stem cells (B10), human kidney stem cells (HEK293 cell), human prostate cancer (Du 145, PC3) and normal human fibroblasts (HS 68) tested. However, HGMNs were cytotoxic at 69.99% against the DU145 prostate cancer cell, and at 34.37% in the Hela cell. These results indicate that the GMNs were biostable and the HGMNs served as effective drug delivery vehicles.

• Journal of Ginseng Research
• /
• v.47 no.5
• /
• pp.627-637
• /
• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• Korean Journal of Bronchoesophagology
• /
• v.14 no.1
• /
• pp.59-64
• /
• 2008

Pure esophageal atresia without tracheoesophageal fistula is a uncommon form of congenital malformation of the esophagus, which is able to be suspected by fetal ultrasonograpy before delivery and diagnosed definitely by simple chest X-ray and esophagogram immidiately after delivery. We performed delayed primary repair in 2 cases of pure esophageal atresia by using stomach for conduit in one case and colon in the other case. But there were graft failure in the latter case, so reoperation was performed by using stomach. Postoperatively, two patients showed no stenosis and leakage in anastomotic site and were discharged in good oral intake without dysphagia.

• Macromolecular Research
• /
• v.17 no.9
• /
• pp.709-713
• /
• 2009

The aim of this study was to develop novel intestinal specific drug delivery systems with pH sensitive swelling and drug release properties. The carboxyl group of ibuprofen was converted to a vinyl ester group by reacting ibuprofen and vinyl acetate as an acylating agent in the presence of catalyst. The glucose-6-acrylate-1, 2, 3, 4-tetraacetate (GATA) monomer was prepared under mild conditions. Cubane-1, 4-dicarboxylic acid (CDA) linked to two 2-hydroxyethyl methacrylate (HEMA) group was used as the crosslinking agent (CA). Methacrylic-type polymeric prodrugs were synthesized by the free radical copolymerization of methacrylic acid, vinyl ester derivative of ibuprofen (VIP) and GATA in the presence of cubane cross linking agent. The structure of VIP was characterized and confirmed by FTIR, $^1H$ NMR and $^{13}C$ NMR spectroscopy. The composition of the cross-linked three-dimensional polymers was determined by FTIR spectroscopy. The hydrolysis of drug polymer conjugates was carried out in cel-lophane membrane dialysis bags, and the in vitro release profiles were established separately in enzyme-free simulated gastric and intestinal fluids (SGF, pH 1 and SIF, pH 7.4). The detection of a hydrolysis solution by UV spectroscopy at selected intervals showed that the drug can be released by hydrolysis of the ester bond between the drug and polymer backbone at a low rate. Drug release studies showed that increasing the MAA content in the copolymer enhances the rate of hydrolysis in SIP. These results suggest that these polymeric prodrugs can be useful for the release of ibuprofen in controlled release systems.

• Macromolecular Research
• /
• v.11 no.4
• /
• pp.291-295
• /
• 2003

Dextran as a candidate material for colon-specific drug delivery has been studied. Crosslinked dextran hydrogels were prepared by mixing dextran, $MgCl_2$, glutaraldehyde (GA) and polyethyleneglycol (PEG 400) in water. The dextran hydrogels were characterized by measuring equilibrium swelling ratios and mechanical strengths. Response surface methodology (Central Composite Design) was used to evaluate the swelling behaviors and mechanical strengths as functions of concentrations of $MgCl_2$, GA, and PEG 400, which was found to be useful for the evaluation. It showed that the swelling behavior and mechanical strengths were influenced significantly by PEG 400 and $MgCl_2$ concentrations.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.1
• /
• pp.283-287
• /
• 2012

Objective: To explore the participation rates for breast and colorectal cancer screening and identify associated correlates among elderly women. Methods: Logistic regressions were conducted using data collected in 2006 from 1,533 elderly women aged 60 years or above who had completed a screening instrument, the Minimum Data Set-Home Care, while applying for long-term care services at the first time in Hong Kong. Results: The participation rates for breast and colorectal cancer screening among frail older Chinese women were 3.7% and 10.8% respectively. Cognitive status was inversely associated with the likelihood of participation in screening (breast: OR = 0.66, 95%CI = 0.47-0.94; colon: OR = 0.81, 95%CI = 0.66-0.99), as was educational level with the likelihood of participation in breast cancer screening (no formal education: OR = 0.20, 95%CI = 0.06-0.61, some primary education: OR = 0.31, 95%CI = 0.10-1.00). Conclusion: The delivery of cancer preventive health services to frail older women is less than ideal. Cognitive status and educational level were important factors in cancer screening behaviour. Tailor-made strategic promotion programmes targeting older women with low cognitive status and educational levels are needed to enhance awareness and acceptance within this vulnerable group.

• Journal of Photoscience
• /
• v.12 no.3
• /
• pp.123-127
• /
• 2005

The polyclonal antibody was generated against the peptide fragment of 62 amino acid residues (D 181-T242) near the COOH-terminal region of the extracellular domain of epithelial-cell adhesion molecule (Ep-CAM) and shown to be able to recognize Ep-CAM in competitive ELISA. Then, sulforhodamine 101 acid chloride (so called Texas red), a fluorescence dye, was conjugated to the affinity-purified anti-Ep-CAM antibody utilizing the reaction between the aliphatic amines of antibody and the sulfonyl chloride of Texas red. The molar ratio of Texas red to antibody was estimated to be approximately 1.86 by measuring optical densities at 280 nm and 596 nm, implying that the two molecules of Texas red at most were conjugated to antibody. The anti-Ep-CAM antibody-Texas red conjugate was then used for immunohistochemistry of CT-26 murine colon carcinoma cells. Based upon the fluorescence microscope images, anti-Ep-CAM antibody is able to deliver Texas red specifically to the surface of CT-26 cells on which Ep-CAM was actively expressed. This result indicates that anti-Ep-CAM antibody could be useful for the tissue-specific delivery of photosensitizers via antigen-antibody interaction.

• Genomics & Informatics
• /
• v.14 no.4
• /
• pp.255-264
• /
• 2016

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

• Journal of Ginseng Research
• /
• v.31 no.1
• /
• pp.1-13
• /
• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.