Chong-Kook Kim

Seoul National University, Seoul, Seoul, South Korea

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Publications (129)378.1 Total impact

  • Su-Eon Jin, Chong-Kook Kim
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    ABSTRACT: Cationic lipid nanoparticles (cLNs) were modified to develop a gene delivery system for topical use via a dermal route. The cLNs were formulated using high pressure homogenization method and were composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioleoylphosphatidylethanolamine (DOPE), Tween 20, and tricaprin as a solid core (1:1:1:1.67, w/w). The prepared cLNs were nanoscale-sized (<100nm) and were highly positive (51mV). The cLN/DNA complexes demonstrated enhanced transfection potential in the cells at the optimal ratio without cytotoxic effects. To evaluate its efficacy in topical application, in vitro skin transfer of the cLN/DNA complexes was monitored using the measurement of the surface zeta potential of hairless mouse skin and validated using confocal microscopy of the sectioned skin. The in vivo delivery of plasmid DNA with the cLN formulation was examined using the relative expression levels of mRNA after non-invasive application with the cLN/DNA complexes on hair-removed dorsal skin of mice. The cLNs successfully transferred plasmid DNA to the skin, which was facilitated by the charge-mediated interaction between the cLN/DNA complexes and the skin. These results suggest the promising potential of cLNs as a topical gene delivery system for gene vaccine delivery and cutaneous gene therapy in preclinical and clinical applications.
    Colloids and surfaces B: Biointerfaces 02/2014; 116C:582-590. · 4.28 Impact Factor
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    ABSTRACT: A selective and sensitive liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of cefdinir in rat plasma and urine. Following a simple protein precipitation using methanol, chromatographic separation was achieved with a run time of 10 min using a Synergi 4 µ polar-RP 80A column (150 × 2.0 mm, 4 µm) with a mobile phase consisting of 0.1% formic acid in water and methanol (65:35, v/v) at a flow rate of 0.2 mL/min. The protonated precursor and product ion transitions for cefdinir (m/z 396.1 → 227.2) and cefadroxil, an internal standard (m/z 364.2 → 208.0) were monitored in the multiple reaction monitoring in positive ion mode. The calibration curves for plasma and urine were linear over the concentration range 10-10,000 ng/mL. The lower limit of quantification was 10 ng/mL. All accuracy values were between 95.1 and 113.0% and the intra- and inter-day precisions were <13.0% relative standard deviation. The stability under various conditions in rat plasma and urine was also found to be acceptable at three concentrations. The developed method was applied successfully to the pharmacokinetic study of cefdinir after oral and intravenous administration. Copyright © 2013 John Wiley & Sons, Ltd.
    Biomedical Chromatography 05/2013; · 1.95 Impact Factor
  • Eunmi Ban, Chong-Kook Kim
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    ABSTRACT: The thermosensitive-mucoadhesive ondansetron liquid suppository (tmOLS) was developed to enhance patient compliance and bioavailability in high-risk patients receiving highly emetogenic therapy and having difficulty in swallowing, The thermosensitive-mucoadhesive liquid suppository bases were formulated using poloxamers (P407 and P188) and hydroxypropylmethyl cellulose (HPMC). The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, mucoadhesive force, rheological properties, and in vitro release. Rectal mucosal damage following rectal administration of tmOLS in rats was assessed using microscopy. Pharmacokinetic analyses were performed to compare tmOLS administered via the rectal route to ondansetron solution administered orally. The liquid suppository base of tmOLS contained P407, P188, and HPMC in the ratio 18:20:0.8, was in the liquid state at room temperature, underwent gelation at body temperature. Area under the curve and half-life (t(1/2)) of ondansetron were significantly higher in the tmOLS-treated group, indicating that the formulation bypassed the first-pass metabolism and that it was released slowly from the tmOLS because of the formation of mucoadhesive gel state. Furthermore, the t(1/2) of tmOLS was two-fold that of the oral solution. Thus, tmOLS could be administered to patients who have difficulty in swallowing; however, adjustments in dosing interval may be needed.
    Archives of Pharmacal Research 02/2013; · 1.54 Impact Factor
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    ABSTRACT: A specific and sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) in the negative electrospray ionization mode was developed and validated in order to analyze 3α-hydroxytibolone (3α-OH-tibolone), major metabolite of tibolone in human plasma sample using only 200 μL of plasma. 3α-OH-tibolone and 3α-OH-tibolone-d6 (internal standard, IS) in plasma were derivatized with p-toluenesulfonyl isocyanate after extraction using ethyl acetate. The dye residue and by-products was excluded using HLB Oasis SPE cartridge after derivertization. Separation of derivatized 3α-OH-tibolone and IS was performed on a C18 column within 6 min. The assay showed linearity in concentration ranges of 0.2–20 ng/mL. Intra-day precision and accuracy ranged from 0.77 to 5.0 % and from 98.0 to 100.56 %, respectively. Inter-assay precision and accuracy ranged from 1.49 to 5.00 % and from 99.75 to 100.94 %, respectively. A specific, reproducible and sensitive LC/MS/MS method for quantification of 3α-OH-tibolone in human plasma was successfully applied to evaluate the bioequivalence of tibolone in human volunteer following single oral administration of 5 mg tibolone.
    Journal of Pharmaceutical Investigation. 12/2012; 42(6).
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    ABSTRACT: We report a green synthesis of silver nanoparticles that uses extracts from the aerial part of Artemisia capillaris. Both water and 70% ethanol extracts successfully generated silver nanoparticles. The formation of silver nanoparticles was confirmed by surface plasmon resonance bands, Fourier transform-infrared spectra, high resolution-transmission electron and atomic force microscopic images. Various shapes of silver nanoparticles were generated with an average diameter of 29.71 nm with water extract and 29.62 nm with 70% ethanol extract. An improvement in antibacterial activity (MIC 8.35-16.7 microg/mL) was observed against a total of twenty different strains of Gram-negative and Gram-positive bacteria. A remarkable enhancement (approximately 12-fold) was observed against Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, Klebsiella oxytoca, and Klebsiella areogenes when compared with the extract alone. Silver nanoparticles produced by the 70% ethanol extract showed slightly higher antibacterial activity than those generated with the water extract. The correlation between total flavonoid content of each extract and the antibacterial activity did not exert any significant relationships. This report suggests that plant extracts have the potential to be used as powerful reducing agents for the production of biocompatible silver nanoparticles possessing enhanced antibacterial activities.
    Journal of Nanoscience and Nanotechnology 09/2012; 12(9):7087-95. · 1.15 Impact Factor
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    ABSTRACT: Two types of radioiodinated plasma driven antigens, heat-inactivated ((125)I-h-HBsAg) and formalin-inactivated HBsAg ((125)I-f-HBsAg) were investigated for the effect of immunoadjuvant, aluminium phosphate (AP) on pharmacokinetics, organ distribution and humoral immunity of differently inactivated hepatitis B surface antigens (HBsAg) in rats. As a result, most of h-HBsAg (90%) was retained and slowly eliminated from the injection site. The h-HBsAg was highly localized in regional lymph node (RLN), but resulted in low humoral immune response. On the other hand, f-HBsAg was less localized in the injection site and RLN, but mainly distributed into serum and liver (62.9 and 22.4%, respectively). However, both h-HBsAg and f-HBsAg slowly disappeared from the injection site with AP, resulting in the increased area under the amount-time curve (AUQ) of h-HBsAg and f-HBsAg in the injection site. Exposures of h-HBsAg and f-HBsAg in serum were increased (1.4 and 2.8 times increase in AUC, respectively) with AP. The RLN uptake of both antigens were dramatically increased (25 and 3.1 times increase in AUC, respectively) with higher humoral immune response. The antibody titres were also increased with AP. In conclusion, pharmacokinetics, organ distribution and humoral immunity of h-HBsAg were highly dependent on the inactivation method of antigen and the presence of immunoadjuvant such as AP.
    Archives of Pharmacal Research 09/2012; 35(9):1621-8. · 1.54 Impact Factor
  • Su-Eon Jin, Chong-Kook Kim, Yang-Bae Kim
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    ABSTRACT: SMAD3 is a key player in the TGFβ signaling pathway as a primary inducer of fibrosis. The inhibition of SMAD3 production is one strategy to alleviate fibrosis in keloid fibroblasts. In the present study, antisense oligonucleotides (ASOs) against SMAD3 were designed to specifically block the expression of SMAD3. The cationic lipid nanoparticles (cLNs) were formulated to enhance an intracellular activity of SMAD3 ASOs in keloid fibroblasts. This formulation was prepared using melt-homogenization method, composed of 3-[N-(N',N'-dimethylaminoethane)-carbamol] cholesterol (DC-Chol), dioleoylphosphatidylethanolamine (DOPE), Tween20, and trimyristin as a lipid core (1:1:1:1.3, w/w). The size and zeta potential of cLNs and cLN/ASO complexes were measured using light scattering. AFM was used to confirm the morphology and the size distribution of cLNs and cLN/ASO complexes. The prepared cLNs had a nano-scale sized spherical shape with highly positive charge, which were physically stable without aggregation during the storage. The cLN/SMAD3 ASO complexes were successfully generated and internalized onto keloid fibroblasts without toxicity. After the treatment with cLN/ASO complexes, SMAD3 was inhibited and collagen type I was also significantly suppressed in keloid fibroblasts. These results suggest that SMAD3 ASOs complexed with cLNs have a therapeutic potential to suppress collagen deposition in fibrotic diseases. Therefore, this strategy might be developed to lead to anti-fibrotic therapies.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2012; 82(1):19-26. · 3.15 Impact Factor
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    ABSTRACT: A simple procedure for measuring lipoprotein lipase activity was developed by using newly formulated substrate with turbidimetry method. The activity of lipoprotein lipase was expressed as Y (value) (%) that was calculated by measuring UV absorbance (600 nm) at two time points (30 sec and 15 min). Lipid emulsions as the substrate and other factors affecting the lipolytic activity of lipase were studied. The optimal conditions for an in vitro experiment were found to be with LIPOMCT as lipid substrate at 37°C in tris-HCl buffer (pH 7.4) in the presence of BSA. To evaluate an in vivo applicability, low molecular weight heparin (LMWH)-containing drug, Sulodexide, was administered to the rats. The serum from LMWH-administered rats was incubated in an optimized analytical condition without BSA. As expected, increasing the amount of LMWH administered led to higher lipase activity. The newly developed method was successfully applied to an in vivo model suggesting the potential to be applicable for the pharmacodynamic studies of commercially available products of LPL analogues in human subjects, and for the diagnosis of acute pancreatitis in the clinical laboratory.
    Archives of Pharmacal Research 06/2012; 35(6):1107-14. · 1.54 Impact Factor
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    ABSTRACT: The resistance to current antibiotics results in the emergence of health-threatening bacteria. Silver nanoparticles are known to exhibit broad-spectrum antibacterial activities without the development of resistance. Herein, we developed a green synthetic method for the preparation of silver nanoparticles with sialyllactose instead of toxic chemicals as a reducing agent, which would improve its therapeutic applicability and increase its biocompatibility. Oven incubation, autoclaving and microwave irradiation methods were applied to prepare the silver nanoparticles. High resolution-transmission electron microscopy and atomic force microscopy images revealed mostly spherical and amorphous silver nanoparticles with an average diameter of 23.64 nm. Fourier Transform-infrared spectra suggest that the N-H amide of sialyllactose might be involved in the binding of silver nanoparticles. Based on thermogravimetric analyses, 2,3-sialyllactose-reduced silver nanoparticles are composed of 54.3 wt% organic components and 45.7 wt% metallic silver. Enhanced antibacterial activities of silver nanoparticles (approximately 8-fold) were observed against Pseudomonas aeruginosa, Escherichia coli and Salmonella typhimurium (minimum inhibitory concentration 16 microg/mL). Next, we employed the use of carbohydrate stabilizers to increase the stability of silver nanoparticles during a freeze-drying process. It was found that sucrose and trehalose were the most effective stabilizers. In addition, silver nanoparticles possessed excellent salt stability as well as on-the-shelf stability in the presence of these stabilizers. Derivatives of sialic acid are known to be anti-influenza agents; therefore, the newly prepared silver nanoparticles may serve as useful antibacterial and antiviral agents to cope with both pathogenic bacteria and viruses in the near future.
    Journal of Nanoscience and Nanotechnology 05/2012; 12(5):3884-95. · 1.15 Impact Factor
  • Su-Eon Jin, Chong-Kook Kim
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    ABSTRACT: Purpose: Long-term stable cationic solid lipid nanoparticles (cSLNs) were formulated to transfer SMAD3 antisense oligonucleotides (ASOs) into the cells to enhance the intracellular activity of the ASOs. The SMAD3 ASOs were designed to block the inflammatory processes linked to TGFβ/SMAD3 pathway. Methods: The cSLN formulation was prepared by high-pressure homogenization method composed of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), dioleoylphosphoethanolamine (DOPE), Tween 20, and tricaprin as a solid lipid core (1:1:1:1.67, w/w). The size and the zeta potential of the prepared cSLNs were measured by light scattering. The cSLN/ASO complexes were generated and introduced into the murine macrophage cells. After the treatment of the complexes, the cellular uptake of the complexes was determined by flow cytometry and the intracellular activity of SMAD3 ASOs from the complexes was evaluated by western blotting of SMAD3. In addition, TGFβ1, an upstream molecule of TGFβ/SMAD3 pathway, was monitored by ELISA. Results: The nano-scale sized cSLNs were positively charged and physically stable at 4oC during the storage up to 24 months. The uptake efficiency of the cSLN/ASO complexes into macrophage cells was enhanced up to 80% without cytotoxicity. After the treatment of the cSLN/ASO complexes, SMAD3 as well as TGFβ1 was significantly suppressed based on the SMAD3 ASO activity in the macrophage cells. In addition, the cSLN/ASO complexes prevented the morphological change to dendritic shape in the activated macrophage cells. Conclusion: These results suggest that the cSLNs have a potential to deliver the SMAD3 ASOs to intracellular compartments for the anti-inflammatory effect. The development of this strategy might lead to anti-inflammatory and anti-fibrotic therapies in immunological disorders. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
    Journal of Pharmacy and Pharmaceutical Sciences 05/2012; 15(3):467-82. · 2.20 Impact Factor
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    ABSTRACT: Since women with climacteric syndrome have significantly lower serum levels of estradiol and other related hormones, hormone replacement therapies (HRT) such as estrogen are needed to lessen symptoms. However, HRT can often cause severe adverse effects that include many cancers and stroke. Therefore, new and novel approaches to relieve climacteric syndrome still need to be developed. The aim of this study was to identify biologically active peptides from calf spleen that are responsible for stimulating biosynthesis of steroid hormone and to explore the potential of isolated peptides as therapeutic agents for menopausal syndrome. The reverse phase HPLC system was used to isolate active compounds from calf spleen extract, a cell culture system was used to screen the activity of stimulating hormone secretion, and Matrix-Assisted Laser Desorption/Ionization (MALDI) mass spectrometry was used for molecular weight determination. In the present study, two calf steroidogenic peptides, CSP-1 (MW; 4.655 kDa) and CSP-2 (MW; 8.331 kDa), were isolated and identified from calf spleen and may be putative climacteric syndrome therapeutic agents.
    Archives of Pharmacal Research 03/2012; 35(4):653-8. · 1.54 Impact Factor
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    ABSTRACT: For the buccal drug delivery, chitosan (CS) can be used to improve drug absorption and reduce application frequency and drug amount. The aim of this study is to develop and evaluate mucoadhesive ondansetron buccal films for the treatment of emesis using CS as a mucoadhesive polymer. The film prepared by solvent casting method was comprised of ondansetron (approximately 65 μg)-loaded mucoadhesive gels containing 1, 2 or 3% CS and impermeable backing layer. Rheological property of the gels, physiochemical properties of the films (weight, thickness, drug content, swelling ratio, adhesion time and mucoadhesive force) and in vitro ondansetron release profile from the films were determined to evaluate the formulation. The films containing 3% CS (diameter: 0.5 cm; thickness: 170 μm) was selected as the novel formulation, and were used for the in vivo study. Comparative pharmacokinetic studies of ondansetron with this film and oral solution were performed at the same dose in hamsters. The mean values of T(max) and C(max) of the film and oral solution were similar. However, the half-life, mean residence time and AUC(0-24 h) of the film were about 1.7, 1.4 and 2.0-fold higher than those of the oral solution, respectively. The film showed enhanced bioavailability and prolonged efficacy compared to the oral solution. The mucoadhesive ondansetron buccal film may be a potential alternative to the marketed oral formulation, parenterals and solid suppositories with better patient compliance and higher bioavailability for the treatment of emesis.
    Drug Development and Industrial Pharmacy 12/2011; 38(9):1077-83. · 1.54 Impact Factor
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    ABSTRACT: A sensitive and simple column-switching high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed for the determination of alendronate in human plasma. Alendronate and pamidronate (internal standard, IS) in plasma including Na(2)EDTA were precipitated with sodium hydroxide and calcium chloride after deproteinization using 10% trichloroacetic acid solution. The precipitated alendronate and IS were reconstituted by sodium citrate and citric acid and then derivatized with 9-fluorenylmethyl chloroformate. The resulting solution was injected onto an HPLC system consisting of a pretreatment column and an analytical column, which were connected with a six-port switching valve. The assay was linear in the concentration range of 2-100 ng/mL in 1 mL of plasma with high precision and accuracy, and the limit of detection was 0.5 ng/mL. It was successfully applied to evaluate the pharmacokinetic parameters of alendronate in human volunteers following single oral administration. The mean value of maximum alendronate plasma concentration (C(max)) was 37.69 ng/mL, and the mean time to reach the C(max) (T(max)) was 1.08 h. The area under the plasma concentration-time curve (AUC) and elimination half-life (T(1/2)) were 106.48 ng/mL/h and 1.66 h, respectively.
    Archives of Pharmacal Research 12/2011; 34(12):2079-86. · 1.54 Impact Factor
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    ABSTRACT: To develop the long acting nifedipine oral delivery with bioavailability enhancement, a nifedipine dry elixir (NDE) containing nifedipine ethanol solution in dextrin shell was prepared using a spray-dryer, and then coated nifedipine dry elixir (CNDE) was prepared by coating NDE with Eudragit acrylic resin. The physical characteristics and bioavailability of NDE and CNDE were evaluated, and then compared to those of nifedipine powder. NDE and CNDE, which were spherical in shape, had about 6.64 and 8.68-8.75 μm of geometric mean diameters, respectively. The amount of nifedipine dissolved from NDE for 60 min increased about 7- and 40-fold compared to nifedipine powder in pH 1.2 simulated gastric fluid and pH 6.8 simulated intestinal fluid, respectively. Nifedipine released from CNDE was retarded in both dissolution media compared with that from NDE. After oral administration of NDE, the C(max) and AUC(0→8h) of nifedipine in rat increased about 13- and 7-fold, respectively, and the Tmax of nifedipine was reduced significantly compared with those after oral administration of nifedipine powder alone. The AUC(0→8h) and T(max) of nifedipine in CNDE increased markedly and the C(max) of nifedipine in CNDE was significantly reduced compared to those in NDE. It is concluded that CNDE, which could lower the initial burst-out plasma concentration and maintain the plasma level of nifedipine over a longer period with bioavailability enhancement, might be one of potential alternatives to the marketed long acting oral delivery system for nifedipine.
    Archives of Pharmacal Research 10/2011; 34(10):1711-7. · 1.54 Impact Factor
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    ABSTRACT: To evaluate the effect of subconjunctivally injected liposome-encapsulated tissue plasminogen activator (tPA) on the absorption rate of subconjunctival hemorrhages (SHs). SHs were induced in 1 eye each of 36 rabbits by subconjunctival injection of 0.05 mL of autologous blood. After 8 hours, randomized subconjunctival injections were performed: 26,000 IU/mL liposome-encapsulated tPA (0.05 mL) in 9 eyes (group A), free-form tPA (26,000 IU/mL; 0.05 mL) in 9 eyes (group B), only liposomes (0.05 mL) in 9 eyes (group C), or no injection in 9 eyes (group D). The sizes of the SHs at 8, 24, 48, 72, 96, and 120 hours after induction were measured using an image analyzer and were compared among the 4 groups. Group A showed significantly more rapid absorption rates than all the other groups at 24, 48, and 72 hours and had the significantly shortest mean elapsed time for the complete resorption of SHs. The tPA activity in ocular tissue except conjunctiva and plasma were negligible beyond 24 hours after SH induction with both forms of tPA. In the conjunctiva, the tPA activity was significantly prolonged in the liposome-encapsulated tPA group than in the free tPA group. Subconjunctival injection of liposome-encapsulated tPA seems to enhance SH absorption in rabbits, especially during the early stages with minimal systemic and ocular absorption.
    Cornea 09/2011; 30(12):1455-60. · 1.75 Impact Factor
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    ABSTRACT: 5-Aminolevulinic acid (5-ALA), inducing photodynamic protoporphyrin (PpIX), is a hydrophilic molecule, resulting in leashing the capacity to cross tissue barriers like stratum corneum (SC) of skin. Here, we aimed to develop 5-ALA loaded ultradeformable liposomes (UDL) with different surface charges, and to investigate their physicochemical characteristics and capability for the skin penetration and retention of 5-ALA for topical photodynamic therapy (PDT). The effects of surface charges of UDL on in vitro permeation of 5-ALA and in vivo accumulation of 5-ALA-induced PpIX in viable skin were determined and then compared with conventional neutral liposomes (nLiposome). All UDL showed smaller particle size and better deformability than nLiposome. However, entrapment efficiency of 5-ALA was similar to each vesicle. Among vesicles, the cationic UDL (cUDL) demonstrated higher stability and permeability, and could deliver 5-ALA into deep skin tissue by topical application. Moreover, the 5-ALA loaded in cUDL was long retained, and induced more amount of PpIX in viable skin than those in other UDL and nLiposome. Considering that the conversion of 5-ALA into PpIX occurs preferentially in epidermis, these results suggested that topical delivery of 5-ALA loaded in cUDL could be an interesting proposal to optimize PDT related to 5-ALA.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 09/2011; 44(1-2):149-57. · 2.61 Impact Factor
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    ABSTRACT: Green-synthesized gold nanoparticles were utilized for the detection of organophosphorous pesticides. Heparin, one of glycosaminoglycans, was used as a reducing and stabilizing agent. The reaction conditions were optimized, and high resolution-transmission electron microscopic images revealed gold nanoparticles of various shapes. Organophosphorous pesticides in water were detected by simply mixing them with gold nanoparticles. NaCl induced a color change in the mixed solution from wine-red to purple-blue that was dependent on the pesticide concentration in the range of 10-1,000 ppb. Gold nanoparticles were immobilized on a silica gel matrix in order to prepare solid supports for removing pesticides. The incorporation of atomic gold and heparin bound to 2 g of silica gel was determined 4,058 ppm and 33 microg as measured by inductively coupled plasma-atomic emission spectrophotometry and carbazole assay, respectively. AuNPs-immobilized silica gel columns were successfully applied for removing fenthion in water confirmed by RP-HPLC and FT-IR analyses.
    Journal of Nanoscience and Nanotechnology 09/2011; 11(9):7570-8. · 1.15 Impact Factor
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    ABSTRACT: The objective of this study was to achieve an optimal formulation of dexibuprofen dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To control the release rate of dexibuprofen, Eudragit(®) RS was employed on the surface of DDE resulting in coated dexibuprofen dry elixir (CDDE). Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and contents of dexibuprofen and ethanol were characterized. Pharmacokinetic parameters of dexibuprofen were evaluated in the rats after oral administration. The DDE and CDDE were spherical particles of 12 and 19 μm, respectively. The dexibuprofen and ethanol contents in the DDE were dependent on the amount of dextrin and maintained for 90 days. The dissolution rate and bioavailability of dexibuprofen loaded in dry elixir were increased compared with those of dexibuprofen powder. Moreover, coating DDE with Eudragit(®) RS retarded the dissolution rate of dexibuprofen from DDE without reducing the bioavailability. Our results suggest that CDDE may be potential oral dosage forms to control the release and to improve the bioavailability of poorly water-soluble dexibuprofen.
    International Journal of Pharmaceutics 02/2011; 404(1-2):301-7. · 3.99 Impact Factor
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    ABSTRACT: A sensitive and selective reverse-phase liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) method was developed and validated to quantify pseudoephedrine (CAS 90-82-4) in human plasma. Phenacetin was used as the internal standard (I.S.). Sample preparation was performed with a deproteinization step using acetonitrile. Pseudoephedrine and I.S. were successfully separated using gradient elution with 0.5% trifluoroacetic acid (TFA) in water and 0.5% TFA in methanol at a flow-rate of 0.2 mL/min. Detection was performed on a single quadrupole mass spectrometer by a selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The ESI source was set at positive ionization mode. The ion signals of m/z 166.3 and 180.2 were measured for the protonated molecular ions of pseudoephedrine and I.S., respectively. The lower limit of quantification (LLOQ) of pseudoephedrine in human plasma was 10 ng/mL and good linearity was observed in the range of concentrations 10-500 ng/mL (R2 = 1). The intra-day accuracy of the drug containing plasma samples was more than 97.60% with a precision of 3.99-11.82%. The inter-day accuracy was 99.36% or more, with a precision of 7.65-18.42%. By using this analytical method, the bioequivalence study of the pseudoephedrine preparation was performed and evaluated by statistical analysis of the log transformed mean ratios of pharmacokinetic parameters. All the results fulfilled the standard criteria of bioequivalence, being within the 80-125% range which is required by the Korea FDA, US FDA, and EMEA to conclude bioequivalence. Consequently, the developed reverse-phase LC-ESI-MS method was successfully applied to bioequivalence studies of pseudoephedrine in healthy male volunteers.
    Arzneimittel-Forschung 01/2011; 61(5):276-81. · 0.56 Impact Factor
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    ABSTRACT: Low molecular weight heparin (LMWH)-loaded flexible liposomes (flexosomes) were formulated for transdermal delivery, and their physicochemical and pharmacokinetic parameters were compared with LMWH-loaded ethosomes. Flexosomes had similar particle size compared with ethosomes, but their deformability was higher than that of ethosomes (76.7% vs. 46.8%). In vitro, flexosomes demonstrated 2.6-fold higher permeability coefficient than ethosomes. In comparison to LMWH aqueous solution, skin deposition of flexosome increased 3.2-fold, while that of ethosome increased only 2.0-fold. In vivo, after the topical application of flexosome to hairless mouse, [anti-Xa](max) was 1.11 IU/mL, while ethosomes showed only 0.32 IU/mL. Moreover, AUC(0-24 h) of flexosomes was 2.5-fold higher than ethosomes. In conclusion, the enhanced skin permeation and bioavailability of LMWH can be achieved with flexosomes in comparison with ethosomes. The LMWH transdermal delivery via flexosomes has the potential to replace the parenteral dosage forms for the treatment of venous thromboembolism, pulmonary embolism and cardiovascular events.
    Journal of Microencapsulation 01/2011; 28(3):151-8. · 1.57 Impact Factor

Publication Stats

2k Citations
378.10 Total Impact Points

Institutions

  • 1989–2013
    • Seoul National University
      • College of Pharmacy
      Seoul, Seoul, South Korea
  • 2012
    • Korea Institute of Toxicology
      Sŏul, Seoul, South Korea
  • 2011
    • Seoul National University Bundang Hospital
      • Department of Ophthalmology
      Seoul, Seoul, South Korea
  • 2009
    • Kim's Eye Hospital
      Sŏul, Seoul, South Korea
    • Korea University
      • College of Medicine
      Seoul, Seoul, South Korea
  • 2006–2009
    • Seoul National University Hospital
      • Department of Ophthalmology
      Seoul, Seoul, South Korea
  • 1995–2008
    • Chungnam National University
      • College of Pharmacy
      Seongnam, Gyeonggi, South Korea
  • 2005–2007
    • Catholic University of Korea
      • • Department of Obstetrics and Gynecology
      • • Cancer Research Institute
      Seoul, Seoul, South Korea
  • 2003–2005
    • Yeungnam University
      • College of Pharmacy
      Asan, South Chungcheong, South Korea
  • 2004
    • National Cancer Center Korea
      Kōyō, Gyeonggi Province, South Korea
  • 2003–2004
    • CHA University
      • College of Medicine
      Seoul, Seoul, South Korea