The Blood and Tissue Distribution of Paclitaxel after Oral Administration of Mucoadhesive Formulation

Hesson Chung,Seo Young Jeong,Ick Chan Kwon,Yeong Tack Park,Young Hak Kwak,In Hyun Lee,Jung Wan Hong 大韓藥學會 2004 大韓藥學會 總會 및 學術大會 Vol.2004 No.1

Paclitaxel formulations for oral administration were prepared. These liquid type oily formulations can be taken as is without dilution. Preliminary studies show that oral formulation had superior antitumor efficacy and high bioavailability. The tissue distribution of paclitaxel was determined after peroral administration of mucoadhesive paclitaxel formulation. The paclitaxel formulation comprising monoglyceride, triglyceride and tween 80 was administered orally to female Balb/c mice. After the administration, paclitaxel was widely distributed in various organs, and maximum drug levels were achieved in 2 h in most tissues. The paclitaxel concentration was the highest in the liver. More than 5 % of the administered drug was found in this organ.

Stability and Degradation Products of 3-Bromopyruvate, a Newly Found Anticancer Drug

CHUNG Hesson,SUNG Ha Chin,KWON Ick Chan,KIM Tae Hyung 대한약학회 2006 大韓藥學會 總會 및 學術大會 Vol.2006 No.2

유전자 치료와 분자영상의학

정혜선,권익찬,정서영 대한의사협회 2004 대한의사협회지 Vol.47 No.2

Absorption mechanism of DHP107, an oral paclitaxel formulation that forms a hydrated lipidic sponge phase

Jang, Yura,Chung, Hye Jin,Hong, Jung Wan,Yun, Cheol-Won,Chung, Hesson Springer Science and Business Media LLC 2017 Acta pharmacologica Sinica. Vol.38 No.1

<P>Paclitaxel is a most widely used anticancer drug with low oral bioavailability, thus it is currently administered via intravenous infusion. DHP107 is a lipid-based paclitaxel formulation that can be administered as an oral solution. In this study, we investigated the mechanism of paclitaxel absorption after oral administration of DHP107 in mice and rats by changing the dosing interval, and evaluated the influence of bile excretion. DHP107 was orally administered to mice at various dosing intervals (2, 4, 8, 12, 24 h) to examine how residual DHP107 affected paclitaxel absorption during subsequent administration. Studies with small-angle X-ray diffraction (SAXS) and cryo-transmission electron microscopy (cryo-TEM) showed that DHP107 formed a lipidic sponge phase after hydration. The AUC values after the second dose were smaller than those after the first dose, which was correlated to the induction of expression of P-gp and CYP in the livers and small intestines from 2 h to 7 d after the first dose. The smaller AUC value observed after the second dose was also attributed to the intestinal adhesion of residual formulation. The adhered DHP107 may have been removed by ingested food, thus resulting in a higher AUC. In ex vivo and in vivo mucoadhesion studies, the formulation adhered to the villi for up to 24 h, and the amount of DHP107 that adhered was approximately half that of monoolein. The paclitaxel absorption after administration of DHP107 was not affected by bile in the cholecystectomy mice. The dosing interval and food intake affect the oral absorption of paclitaxel from DHP107, which forms a mucoadhesive sponge phase after hydration. Bile excretion does not affect the absorption of paclitaxel from DHP107 in vivo.</P>

Single and Two-Week Repeated Oral Dose Toxicity Study of DHP2, a Hydrophobic Drug Delivery Vehicle in Mice

Junghee Han,Hesson Chung,Jong-Hwa Lee,Jeong-Eun Suh,Gab-Soo Lee,Jong-Choon Kim,Boo-Hyon Kang 한국독성학회 2004 Toxicological Research Vol.20 No.1

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals<br/> treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

Single and Two-Week Repeated Oral Dose Toxicity Study of DHP2, a Hydrophobic Drug Delivery Vehicle in Mice

Junghee Han,Hesson Chung,Jong-Hwa Lee,Jeong-Eun Suh,Gab-Soo Lee,Jong-Choon Kim,Boo-Hyon Kang 한국독성학회 2004 Toxicological Research Vol.20 No.2

The present study was conducted to investigate the single and 2-week repeated dose toxicity of DHP2, a hydrophobic drug delivery vehicle, in ICR mice. The test article was administered orally to mice at the dose levels of 2.5, 12.5 and 37.5 g/kg for single dose toxicity study and at the dose levels of 0, 2.5, 5, and 10 g/kg for repeated dose toxicity study. In both studies, there were no treatment-related effects on mortality, clinical signs, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights of all animals<br/> treated DHP2. Based on these results, it was concluded that the 2-week repeated oral dose of DHP2 may have no toxic effect in mice at a dose level of 10 g/kg. In the condition of this study, the no-observed-adverse-effect level (NOAEL) was considered to be 10 g/kg/day for both sexes.

FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

Park, Hee Sun,Chung, Jin Wook,Jae, Hwan Jun,Kim, Young Il,Son, Kyu Ri,Lee, Min Jong,Park, Jae Hyung,Kang, Won Jun,Yoon, Jung Hwan,Chung, Hesson,Lee, Kichang unknown 2007 KOREAN JOURNAL OF RADIOLOGY Vol.8 No.3

<P><B>Objective</B></P><P>We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model.</P><P><B>Materials and Methods</B></P><P>VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology.</P><P><B>Results</B></P><P>The SUV of the VX2 tumors before treatment (3.87 ±1.51 [mean ±SD]) was significantly higher than that of nontumorous liver parenchyma (1.72 ±0.34) (<I>p</I> < 0.0001, Mann-Whitney <I>U</I> test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05 ±1.21) (<I>p</I> = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41 ±0.73) than that before treatment (<I>p</I> = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48% ±15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range.</P><P><B>Conclusion</B></P><P>Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.</P>

Injectable Gel Type Formulation of Hydrated Egg Phosphatidylcholine and Hyaluronate for Local Drug Delivery

Kim, Sang Gyun,Chung, Hesson,Lee, In Hyun,Kang, Seung Back,Kwon, Ick Chan,Sung, Ha Chin,Jeong, Seo Young 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.3

Injectable gel composed of egg phosphatidylcholine (egg PC), hyaluronate (HA) and water was formulated for local drug delivery. The lamellar liquid crystalline structure of the eg PC/water system did not change by adding HA in the formulation. However, egg PC/HA/water gel was more resistant to erosion than the egg PC/water gel. The egg PC/HA/water and egg PC/water gels containing model drugs, tetracycline and sudan Ⅳ were prepared to perform I vitro and in vivo drug release experiments. In vitro release of tetracycline was sustained in the gel type formulations. The release rate of hydrophobic sudan Ⅳ was extremely slow. More than 99% of sudan Ⅳ remained inside the gel after 5 days. In vivo release of drugs from the air pouch model in Balb/c mice shows that lipophilic sudan Ⅳ remained for more that 10 days whereas tetracycline remained for 1 day in the pouch. The compatibility of the gels was also examined by histopathology. The gels did not cause any adverse inflammatory effect in the air pouch.

In vitro cellular interaction and absorption of dispersed cubic particles

Um, Jung Yoon,Chung, Hesson,Kim, Kil Soo,Kwon, Ick Chan,Jeong, Seo Young 梨花女子大學校 藥學硏究所 2003 藥學硏究論文集 Vol.- No.12

A precursor type oily liquid formulation comprising monoolein, Phironic F-127 and ethanol has been prepared as a carrier for lipophilic drugs. When dispersed in water, the liquid precursor formulation produces sub-micron (200-500 nm) sized lipid particles, named 'nanocubicles'. The interaction between nanocubicles and Caco-2 cell was studied, and the absorption of nanocubicles by cells was observed by various microscopic techniques. Lipid droplets were observed in cytosol after incubation with nanocubicles with time. The degree of pyrene absorption encapsulated in nanocubicles was dependent on particle size and incubation time. The amount of pyrene absorbed by Caco-2 cells was ca. 20% of total at 37 ℃ after an 8-h incubation. When nanocubicles with a bigger average particle size (ca. 600 nm) were applied, the uptake rate was reduced to 10% under identical experimental conditions. The nanocubicles were easily solubilized by bile salts to produce mixed micelles. As bile salt concentration increased, pyrene absorption into the jejunum of rat everted sac in vitro increased.

Airway gene transfer using cationic emulsion as a mucosal gene carrier

Kim, Tae Woo,Chung, Hesson,Kwon, Ick Chan,Sung, Ha Chin,Shin, Byung Chul,Jeong, Seo Young John Wiley Sons, Ltd. 2005 The journal of gene medicine Vol.7 No.6

<B>Background</B><P>Delivery of genes to airway mucosa would be a very valuable method for gene therapy and vaccination. However, there have been few reports on suitable gene delivery systems for administration. In this study, we use a cationic emulsion system, which is physically stable and facilitates the transfer of genes in the presence of up to 90% serum, as a mucosal gene carrier.</P><B>Methods and results</B><P>Cationic lipid emulsion was formulated with squalene and 1,2-dioleoyl-sn-glycero-3-trimethylammoniumpropane (DOTAP) as major components. Emulsions formed stable complexes with DNA and protected and transferred DNA to target cells against DNase I digestion in the presence of mucosal destabilizers such as heparin sulfate (a polysaccharide of the glycosaminoglycan family in mucosa) and Newfectan (a natural lung extract of bovine) in an in vitro system. In contrast, commercial liposomes and counter liposomes, made with an identical lipid composition of emulsions, failed. After in vivo intranasal instillation, the cationic emulsion showed at least 200 times better transfection activity than the liposomal carriers in both nasal tissue and lung.</P><B>Conclusions</B><P>These findings show that cationic emulsions can mediate gene transfection into airway epithelium, making it a good choice for transferring therapeutic genes and for genetic vaccination against an pathogenic infection via an airway route. Copyright © 2005 John Wiley & Sons, Ltd.</P>