Utah Inha and Advanced Therapeutics Research Center

Incheon, South Korea

Utah Inha and Advanced Therapeutics Research Center

Incheon, South Korea

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Ramasamy T.,Utah Inha and Advanced Therapeutics Research Center | Ramasamy T.,Vels University | Ramasamy T.,P.A. College | Khandasami U.S.,P.A. College | And 3 more authors.
Macromolecular Research | Year: 2012

The aim of this study was to formulate and evaluate Ketoconazole-loaded solid lipid nanoparticles (KSLN) for topical application. The purpose of this study was to improve the therapeutic activity of Ketoconazole. KSLN was prepared by a hot homogenization method and characterized for shape, surface morphology, particle size, drug entrapment, cytotoxicity, and rheological analysis. The optimized formulation of solid lipid nanoparticles (SLN) was spherical in shape with a smooth surface and possessed an average size of 172.2±0.75 nm with zeta potential of -44.12±0.76 mV. To guarantee the stability of the desired SLN, they were lyophilized using cryo-protectants. The particle size of the SLN significantly enlarged for formulations which were lyophilized without the cryo-protectants. Cell viability assay performed on National Institute of Health-3-day transfer, inoculum 3×105 cells (NIH-3T3) fibroblast cells showed that properties of the SLN remain unchanged during the process of freeze-drying and were not cytotoxic. An in vitro drug release study showed that KSLN-incorporated hydrogel exhibited a sustained drug release comparing to KSLN dispersion and Ketoconazole loaded hydrogel over a 24 h period. The in vivo studies suggested that the KSLN-incorporated hydrogel was more efficient in the treatment of candidiasis. It may therefore be interpreted that the KSLN-incorporated hydrogel provides a sustained release of Ketoconazole for topical fungal infections and might be a promising delivery system to enhance the therapeutic activity of Ketoconazole.

Jang S.I.,Yonsei University | Kim J.-H.,Yonsei University | Kim M.,Utah Inha and Advanced Therapeutics Research Center | Yang S.,Utah Inha and Advanced Therapeutics Research Center | And 8 more authors.
Endoscopy | Year: 2012

Background and study aim: Metal stents for malignant biliary obstruction are susceptible to occlusion by tumor ingrowth or overgrowth. Therefore, we previously reported our use of a metal stent covered with a paclitaxel- incorporated membrane giving an antitumor effect to prevent occlusion from tumor ingrowth. We have also developed a new generation of paclitaxel-eluting biliary stent using a membrane containing Pluronic F-127 for effective drug delivery. The aim of this study was to investigate the safety and efficacy of drug delivery for this newly developed stent in the biliary tract. Methods: Metal stents were coated with paclitaxel and various concentrations of Pluronic F-127 in phosphate-buffered saline solution. Stents containing varying concentrations were placed in the bile ducts of eight pigs divided as follows: group I, 0 % Pluronic + 0 % paclitaxel; group II, 0 % Pluronic + 10 % paclitaxel; group III, 10 % Pluronic + 10 % paclitaxel; group IV, 20 % Pluronic + 10 % paclitaxel. The histology of the porcine bile duct and the amount of paclitaxel in the porcine serum were examined. The amount of paclitaxel released was also measured in vitro. Results: Histologic changes in the porcine biliary epithelium were acceptable in terms of safety, based on inflammatory cell infiltration and fibrotic reaction. No significant differences in histology were observed between the groups. In the porcine serum analysis, released paclitaxel was detected for 28 days with the 10 % Pluronic concentration (group III). However, released paclitaxel was observed for only 7 days in groups II and IV. In the in vitro experiments, long-lasting release of paclitaxel was also noted from the stent with 10 % Pluronic. Conclusions: The new paclitaxel-eluting stent with 10 % Pluronic F-127 is safe and provides enhanced local drug delivery. © Georg Thieme Verlag KG Stuttgart - New York.

Nadithe V.,University of Utah | Bae Y.H.,University of Utah | Bae Y.H.,Utah Inha and Advanced Therapeutics Research Center
International Journal of Biological Macromolecules | Year: 2010

Hemoglobin (Hb) conjugated with the antioxidant enzymes (SOD and CAT), by employing dicarboxymethylated poly(ethylene glycol), was designed for protection of hemoglobin against free radicals. In this study, the conjugation process was confirmed by employing SDS-PAGE and SEC techniques. The average molecular weight of the conjugates was estimated to be around 1000. kDa. The enzymatic activities of the SOD and CAT in the conjugates (Hb-SOD-CAT) after conjugation were found to retain greater than 70% and 90% of the original bioactivity. Results show that antioxidant enzymes helped minimize methemoglobin (non-carrier of oxygen) formation during the conjugation process and also during storage at 4 °C over a period of 1 month. In summary, the optimized (1:10 Hb/PEG) crosslinked conjugates with antioxidant enzymes showed protective properties from severe free radical stresses when incubated with hydrogen peroxide (0.1 and 1. mM) and xanthine (1. mM)/xanthine oxidase (10 and 20. mU/ml) system © 2010 Elsevier B.V.

Stirland D.L.,University of Utah | Nichols J.W.,University of Utah | Jarboe E.,University of Utah | Adelman M.,University of Utah | And 4 more authors.
Journal of Controlled Release | Year: 2015

This project uses an ex vivo human perfusion model for studying transport in benign, fibrous tumors. The uterine arteries were cannulated to perfuse the organ with a buffer solution containing blood vessel stain and methylene blue to analyze intratumoral transport. Gross examination revealed tissue expansion effects and a visual lack of methylene blue in the fibroids. Some fibroids exhibited regions with partial methylene blue penetration into the tumor environment. Histological analysis comparing representative sections of fibroids and normal myometrium showed a smaller number of vessels with decreased diameters within the fibroid. Imaging of fluorescently stained vessels exposed a stark contrast between fluorescence within the myometrium and relatively little within the fibroid tissues. Imaging at higher magnification revealed that fibroid blood vessels were indeed perfused and stained with the lipophilic membrane dye; however, the vessels were only the size of small capillaries and the blood vessel coverage was only 12% that of the normal myometrium. The majority of sampled fibroids had a strong negative correlation (Pearson's r = - 0.68 or beyond) between collagen and methylene blue staining. As methylene blue was able to passively diffuse into fibroid tissue, the true barrier to transport in these fibroids is likely high interstitial fluid pressure, correlating with high collagen content and solid stress observed in the fibroid tissue. Fibroids had an average elevated interstitial fluid pressure of 4 mm Hg compared to - 1 mm Hg in normal myometrium. Our findings signify relationships between drug distribution in fibroids and between vasculature characteristics, collagen levels, and interstitial fluid pressure. Understanding these barriers to transport can lead to developments in drug delivery for the treatment of uterine fibroids and tumors of similar composition. © 2015, Elsevier B.V. All rights reserved.

Nadithe V.,University of Utah | Bae Y.H.,University of Utah | Bae Y.H.,Utah Inha and Advanced Therapeutics Research Center
Tissue Engineering - Part A | Year: 2011

A low p50 hemoglobin (Hb) (p50 indicates O2 tension at which Hb is half-saturated)-based oxygen carrier conjugated to antioxidant enzymes via dicarboxymethylated poly(ethylene glycol) (PEG) linker may have the beneficial effect in protecting pancreatic beta cells from severe hypoxia at transplantation sites. In this study, the oxygen dissociation curves, Hill plots, Bohr Effect, and oxygen content of Hb conjugates were measured. The protective effect due to incubation of Hb-conjugates (Hb/PEG molar ratio 1:10) with pancreatic beta cells (RINm5F) against hypoxia (6%, 3%, and 1% oxygen) was evaluated by an MTT assay and confocal microscopy. Quantitatively, Hb conjugates with antioxidant enzymes offered statistically significant protection (p<0.01, increased viability ∼80%) from hypoxia compared to control cells in 1% oxygen environment. Confocal images also showed that the low p50Hb conjugates with antioxidants protected RINm5F cells from hypoxia. © 2011 Mary Ann Liebert, Inc.

Jin Y.-J.,Inha University | Jeong S.,Inha University | Lee D.H.,Inha University | Lee D.H.,Utah Inha and Advanced Therapeutics Research Center
Gastrointestinal Endoscopy | Year: 2016

Background/Aims: The aim of this study was to assess the feasibility of needle-knife fistulotomy (NKF) as an initial procedure for biliary access in patients with stones in the common bile duct (CBD) who were at increased risk for post-ERCP pancreatitis (PEP). Method: Fifty-five patients who underwent ERCP with NKF for CBD stones at our institution between July 2013, and May 2015, were prospectively enrolled in this study. They had one or more of the following risk factors for PEP: young age (<60 years), female sex, or normal CBD diameter (≤9 mm). The procedure was performed by an expert biliary endoscopist (S.J.). The success rate of biliary cannulation and CBD stone removal, and the incidence rate of adverse events were assessed. Results: Seventeen patients had 1 risk factor for PEP, 27 had 2, and 11 had 3. The median procedure times for NKF and CBD stone removal after NKF were 2.1 minutes (range, 0.2-8.7 min) and 6.5 minutes (range, 1.1-28.3 min), respectively. Success rates of CBD cannulation and stone removal using NKF were 96.3% (53/55) and 92.7% (51/55), respectively. None of the patients experienced PEP. Retroperitoneal duodenal perforation occurred in 1 patient (1.8%), but it was successfully treated by conservative management. Conclusion: NKF might be feasible as an initial procedure for biliary access in patients with CBD stones who are at high risk for PEP if the procedure is performed by an expert biliary endoscopist. (Clinical trial registration number: KCT0001698.). © 2016 American Society for Gastrointestinal Endoscopy.

Kim M.,Inha University | Kim M.,Utah Inha and Advanced Therapeutics Research Center | Yang S.-G.,Utah Inha and Advanced Therapeutics Research Center | Kim J.M.,Inha University | And 3 more authors.
International Journal of Molecular Medicine | Year: 2012

Non-alcoholic steatohepatitis (NASH) is characterized by hepatocellular injury and initial fibrosis severity has been suggested as an important prognostic factor of NASH. Silymarin was reported to improve carbon tetrachloride-induced liver fibrosis and reduce the activation of hepatic stellate cells (HSC). We investigated whether silymarin could suppress the activation of HSCs in NASH induced by methionine- and choline-deficient (MCD) diet fed to insulin-resistant rats. NASH was induced by feeding MCD diet to obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with standard chow and served as the control. OLETF rats were fed on either standard laboratory chow, or MCD diet or MCD diet mixed with silymarin. Histological analysis of the liver showed improved non-alcoholic fatty liver disease (NAFLD) activity score in silymarin-fed MCD-induced NASH. Silymarin reduced the activation of HSCs, evaluated by counting α-smooth muscle actin (SMA)-positive cells and measuring α-SMA mRNA expression in the liver lysates as well as in HSCs isolated from the experimental animals. Although silymarin decreased α 1-procollagen mRNA expression in isolated HSCs, the anti-fibrogenic effect of silymarin was not prominent so as to show significant difference under histological analysis. Silymarin increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased tumor necrosis factor (TNF)-α mRNA expression in the liver. Our study suggested that the possible protective effect of silymarin in diet induced NASH by suppressing the activation of HSCs and disturbing the role of the inflammatory cytokine TNF-α.

Park J.-S.,Inha University | Jeong S.,Inha University | Lee D.H.,Inha University | Lee D.H.,Utah Inha and Advanced Therapeutics Research Center
Clinical Endoscopy | Year: 2015

Endoscopic stenting is increasingly being used in the management of gastrointestinal luminal obstruction, and has become the current treatment of choice for the palliation of blockage caused by malignant or benign growths. A variety of stents have been developed to enhance the efficacy of the procedure, and improvements are ongoing. In this article, we review the history of, and recent advances in, gastrointestinal stenting. We describe the rationale behind the design as well as the resulting outcome for each stent type. © 2015 Korean Society of Gastrointestinal Endoscopy.

Ahn S.,Korea Advanced Institute of Science and Technology | Lee I.-H.,Korea Advanced Institute of Science and Technology | Lee E.,Utah Inha and Advanced Therapeutics Research Center | Kim H.,Gwangju Institute of Science and Technology | And 2 more authors.
Journal of Controlled Release | Year: 2013

Despite the therapeutic potential of exendin-4 asa glucagon-like peptide-1 (GLP-1) mimetic for the treatment of type 2 diabetes, its utility has so far been limited because of the low level of patient compliance due to the requirement for frequent injections. In this study, an orally available exendin-4 was produced by conjugating it to low molecular weight chitosan (LMWC). Conjugation between the LMWC and cysteinylated exendin-4 was carried out using a cleavable linker system in order to maximize the availability of the active peptide. The LMWC-exendin-4 conjugate formed a nanoparticle structure with a mean particle size of 101 ± 41 nm through complexation between the positively charged LMWC backbone and the negatively charged exendin-4 of individual conjugate molecules. The biological activity of the LMWC-exendin-4 conjugate was evaluated inanINS-1 cell line. The LMWC-exendin-4 conjugate stimulated insulin secretion in a dose dependent manneras similar as that of native exendin-4. From the pharmacokinetic study after oral administration of the conjugate, a Cmax value of 344 pg/mL and a Tmax of 6 h were observed, and the bioavailability, relative to the subcutaneous counterpart, was found to be 6.4%. Furthermore, the absorbed exendin-4 demonstrated a significantly enhanced hypoglyce-mic effect. These results suggest that the LMWC-exendin-4 conjugate could be used as a potential oral anti-diabetic agent for the treatment of type 2 diabetes. © 2013 Elsevier B.V. All rights reserved.

Jeong Y.-I.,Pusan National University | Kim D.-G.,Utah Inha and Advanced Therapeutics Research Center | Kang D.-H.,Pusan National University
Journal of Chemistry | Year: 2013

We synthesized a block copolymer composed of dextran and methoxy poly(ethylene glycol) (mPEG). To accomplish this, the end group of dextran was modified by reductive amination. The aminated dextran (Dextran-NH2) showed the intrinsic peaks of both dextran at 35.5 ppm and hexamethylene diamine at 12.6 ppm at 1H nuclear magnetic resonance (NMR) spectrum. The amino end group of dextran was conjugated with mPEG to make the block copolymer consisting of dextran/mPEG (abbreviated as DexPEG). The synthesized aminated dextran and DexPEG were characterized using 1H NMR and gel permeation chromatography (GPC). The molecular weight and conjugation yield were estimated by comparing the intensity ratio of the proton peaks of the glucose molecule (4.9 ppm and 3.34.0 ppm) to that of the ethylene group of mPEG (3.7 ppm). Abundant hydroxyl group in the dextran chain can be used as a source of bioactive agent conjugation. © 2013 Young-Il Jeong et al.

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