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Cho, Hyun-Jong,Chong, Saeho,Chung, Suk-Jae,Shim, Chang-Koo,Kim, Dae-Duk Kluwer Academic/Plenum Publishers 2012 Pharmaceutical research Vol.29 No.4
<P>A poly-L-arginine (PLR) and dextran sulfate (DEX)-based nano-sized polyelectrolyte complex (nanocomplex) was developed for epidermal growth factor receptor (EGFR) siRNA delivery for the treatment of head and neck cancer.</P>
Praveen. V. Balimane,Saeho Chong,Karishma Patel,Yong Quan,Julita Timoszyk,한용해,Bonnie Wang,Balvinder Vig,Teresa N. Faria 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.4
The purpose of this study was to investigate the utility of stably transfected MDCK-hPepT1 cells for identifying peptide transporter substrates in early drug discovery and compare the characteristics of this cell line with Caco-2 cells. MDCK-hPepT1, MDCK-mock, and Caco-2 cells grown to confluence on 24-well Transwell‚ were used for this study. Expression levels of different transporter proteins (PepT1, PepT2, P-gp) in these cell lines were assessed by qRTPCR. Permeability studies were conducted in parallel in all the cells with a diverse set of peptide substrates using the optimized experimental condition: 100 µM, apical pH 6.0, basolateral pH 7.4, 2 hr incubation at 37°C. Permeability studies were also conducted with classical P-gp substrates (tested in bi-directional mode) and paracellularly absorbed probes to investigate the differences between the cell lines. As expected, MDCK-hPepT1 cells express significantly higher level of PepT1 mRNA compared to both Caco-2 and MDCK-mock cells. Efflux transporter, P-gp, was expressed adequately in all the cell lines. Permeability studies demonstrated that classical peptide substrates had significantly higher permeability in stably transfected MDCK-hPepT1 cells compared to MDCK-mock and Caco-2 cells. The transfected MDCKhPepT1 cells were qualitatively similar to Caco-2 cells with respect to functional P-gp efflux activity and paracellular pore activity. Stably transfected MDCK-hPepT1 cells have been demonstrated as a viable alternative to Caco-2 cells for estimating the human absorption potential of peptide transporter substrates. These cells behave similar to Caco-2 cells with regards to Pgp efflux and paracellular pore activity but demonstrate greater predictability of absorption values for classical peptide substrates (for which Caco-2 cells under-estimate oral absorption).
Kwak, Eun-Young,Shim, Won-Sik,Chang, Ji-Eun,Chong, Saeho,Kim, Dae-Duk,Chung, Suk-Jae,Shim, Chang-Koo Informa Healthcare 2012 Xenobiotica Vol.42 No.7
<OL><LI><P>The phenomenon known as multiple-drug resistance, whereby anti-cancer agents are expelled from cancer cells, makes it necessary to develop methods that will reliably increase the accumulation of anti-cancer agents within cancer cells. To accomplish this goal, a new model compound, Val-SN-38, was synthesized by introducing valine to SN-38, an active ingredient of irinotecan.</P></LI><LI><P>Val-SN-38 improved intracellular accumulation approximately 5-fold in MCF7 cells, compared with SN-38, and rather than changes in membrane permeability, the amino acid transporter <I>ATB</I><SUP><I>0,+</I></SUP> played a role, whereas the dipeptide transporter <I>PEPT1</I> did not. Other sodium-dependent amino acid transporters, namely <I>ATA1</I>, <I>ATA2</I>, and <I>ASCT2</I>, were unexpectedly involved in the uptake of Val-SN-38 as well. The efflux of Val-SN-38 by major efflux transporters was variably changed, but not significantly.</P></LI><LI><P>In summary, the enhanced accumulation of Val-SN-38 in cancer cells was due to augmented uptake via various amino acid transporters. The results of the present study make a compelling argument in favour of a prodrug concept that can improve intracellular accumulation and take advantage of amino acid transporters without significantly inducing multiple-drug resistance.</P></LI></OL>
Hyaluronic acid derivative-based self-assembled nanoparticles for the treatment of melanoma.
Jin, Yu-Jin,Termsarasab, Ubonvan,Ko, Seung-Hak,Shim, Jae-Seong,Chong, Saeho,Chung, Suk-Jae,Shim, Chang-Koo,Cho, Hyun-Jong,Kim, Dae-Duk Kluwer Academic/Plenum Publishers 2012 Pharmaceutical research Vol.29 No.12
<P>Hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs) were developed for the targeted delivery of doxorubicin (DOX), and their antitumor efficacy for melanoma was evaluated.</P>
Hwang, Hee-Jin,Sohn, Ki-Young,Han, Yong-Hae,Chong, Saeho,Yoon, Sun Young,Kim, Young-Jun,Jeong, Jinseoun,Kim, Sang-Hwan,Kim, Jae Wha The Korean Association of Immunobiologists 2015 Immune Network Vol.15 No.3
We previously reported that 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) accelerates hematopoiesis and has an improving effect on animal disease models such as sepsis and asthma. The effects of PLAG supplementation on immune modulation were assessed in healthy men and women. The objective was to evaluate the effects of PLAG supplementation on immune regulatory functions such as activities of immune cells and cytokine production. A randomized double blind placebo-controlled trial was conducted. Seventy-five participants were assigned to one of two groups; all participants had an appropriate number of white blood cells on the testing day. The PLAG group (n=27) received oral PLAG supplements and the control group (n=22) received oral soybean oil supplements. IL-4 and IL-6 production by peripheral blood mononuclear cells (PBMC) were lower (p<0.001 and p<0.001, respectively) with PLAG than with soybean oil. However, the production of IL-2 and IFN-$\gamma$ by PBMC was unaltered with PLAG supplementation. The B cell proliferation decreased significantly in the PLAG group compared to the soybean oil control (p<0.05). The intake of PLAG in healthy adults for 4 weeks was deemed safe. These data suggest that PLAG has an immunomodulatory function that inhibits the excessive immune activity of immunological disorders such as atopic and autoimmune diseases. PLAG could improve the condition of these diseases safely as a health food supplement.
A Combined Chemoimmunotherapy Approach Using a Plasmid−Doxorubicin Complex
Bagalkot, Vaishali,Lee, In-Hyun,Yu, Mi Kyung,Lee, Eunhye,Park, Saeho,Lee, Jae-Hyuk,Jon, Sangyong American Chemical Society 2009 MOLECULAR PHARMACEUTICS Vol.6 No.3
<P>We report a combined chemoimmunotherapy vehicle consisting of plasmid loaded with doxorubicin and evaluate its efficacy in two different tumor models. A stable complex was formed with a 1300:1 ratio of doxorubicin bound to native plasmid via intercalation. Pharmacokinetics of the complex showed much slower clearance from plasma up to 3 h compared to 10 min for free doxorubicin. In mice bearing NCI-H358 xenografts, lower doses of complex (doxorubicin 0.5 mg/kg, plasmid 4 mg/kg) effectively reduced tumor growth compared to high doses (5 mg/kg) of free doxorubicin (68% versus 77%). Similar results were observed in mice bearing 4T1 murine allografts; the complex (doxorubicin 2 mg/kg, plasmid 8 mg/kg) was effective and caused similar reduction of tumor compared to free doxorubicin (4 mg/kg) (47% versus 46%). The complex showed no signs of severe systemic toxicity or cardiotoxicity compared to the free doxorubicin in mice as indicated by body weights and heart tissue histology. Elevated levels of cytokines (IL-12, IL-6, and IFN-gamma) were observed in serum as well as in tumor tissue after intravenous injection of complex when compared to plasmid or doxorubicin alone. This approach simultaneously delivers both chemotherapeutic and immunotherapeutic agents without time delay, improves pharmacokinetics of the free drug, lowers drug toxicity, upregulates a variety of cytokines, and is effective against different tumors.</P>
Physiologically based pharmacokinetic modeling of SNU-0039, an anti-Alzheimer's agent, in rats.
Lee, Kyeong-Ryoon,Chae, Yoon-Jee,Maeng, Han-Joo,Lee, Jeewoo,Kim, Dae-Duk,Chong, Saeho,Shim, Chang-Koo,Chung, Suk-Jae Kluwer Academic/Plenum Publishers 2011 Journal of pharmacokinetics and pharmacodynamics Vol.38 No.5
<P>The objective of this study was to characterize the systemic and tissue kinetics of 2-(3,4-dimethoxyphenyl)-5-(3-methoxypropyl) benzofuran (SNU-0039), an inhibitor of β-amyloid protein aggregation, in rats. Simultaneous fitting of the data to polyexponential equations indicated that the systemic clearance and steady state volume of distribution were estimated to be 0.0220 l/min/kg and 2.33 l/kg. The clearance and volume of distribution were not dependent on the intravenous dose, in the range from 5 to 20 mg/kg. The tissue (i.e., the brain, liver, kidneys, heart, spleen, lungs, gut, muscle and adipose tissue) to plasma partition coefficients (K(p)) for SNU-0039 in rats ranged from a low of 0.779 0.314 (muscle) to a high of 5.71 1.66 (liver). The recoveries of DMB were less than 1% of the dose for the renal and biliary excretion, indicative of minor involvements of these pathways in overall elimination. The fraction of bound SNU-0039 to plasma protein was approximately 95.9% and the fraction of SNU-0039 distributed to blood cells was approximately 45.3%. Assuming a flow-limited distribution, the simulated concentration profiles for SNU-0039 in the physiologically based pharmacokinetic model were in reasonable agreement with the observed concentrations in plasma and nine tissues in rats.</P>