Biomedical subjects

Chong-Kook Kim

Publications and source records attributed to Chong-Kook Kim.

At least 19 recordsLinked to original sources

PubMed2006

Analysis of carbamazepine and its active metabolite, carbamazepine-10,11-epoxide, in human plasma using high-performance liquid chromatography.

A sensitive method based on high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection was developed for the determination of carbamazepine (CBZ) and one of its active metabolites, carbamazepine-10,11-epoxide (CBZ-E) in human plasma. CBZ, CBZ-E and the internal standard (IS) 10,11-dihydrocarbamazepine were extracted from human plasma into methyl tert-butyl ether. CBZ, CBZ-E and the IS were successfully separated on an RP C18 column with a mobile phase of acetonitrile:methanol:water (18:19:63, v/v/v) and monitored via UV detection at 210 nm. The calibration curves were linear over the concentration ranges of 0.01-10 microg/mL for CBZ and 0.005-5 microg/mL for CBZ-E in human plasma, respectively. The method displayed excellent sensitivity, precision and accuracy, and was successfully applied to the quantification of CBZ and CBZ-E in human plasma after oral administration of a single 200 mg CBZ CR tablet. This method is suitable for bioequivalence studies following single doses given to healthy volunteers.

Carbamazepine↗

PubMed2006

Improvement of bioavailability and photostability of amlodipine using redispersible dry emulsion.

To improve the bioavailability and photostability of poorly water-soluble and photosensitive amlodipine, dry emulsion (DE) was prepared by spray-drying the oil-in-water emulsion of amlodipine. Labrafil M 1944 CS and dextrin were employed as oil phase and matrix material, respectively. Dispersing DE in distilled water formed an emulsion with a mean droplet size 1.4-fold larger than that of the homogenized amlodipine emulsion before spray-drying (0.24 +/- 0.30 microm versus 0.17 +/- 0.02 microm). The mean droplet size of DE remained unchanged during 6-month storage at room temperature. 94.4% versus 33.1% of amlodipine remained intact after 24-h UV irradiation of amlodipine as DE formulation or as powder. These data suggest that DE formulation greatly improved the photostability of amlodipine, as well as increasing the physical stability of emulsion systems. In vitro release of DE was higher than that of amlodipine powder (66% versus 48% release at 60 min). Consequently, DE formulation resulted in 2.6- and 2.9-fold higher Cmax and AUC0-24 h of amlodipine compared after oral administration of amlodipine powder in rats. Our data suggest that the DE may be a potential oral dosage form for amlodipine to improve its bioavailability.

Amlodipine↗

PubMed2006

Stabilization of all-trans retinol by loading lipophilic antioxidants in solid lipid nanoparticles.

Loading of drugs into the solid matrix of solid lipid nanoparticles (SLNs) can be one of effective means to protect them against chemical degradation. In this study, the SLNs for all-trans retinol (AR) were formulated to improve the stability of AR, whose chemical instability has been a limiting factor in its clinical use. First of all, the physicochemical properties of AR-loaded SLNs, including mean particle diameter and zeta potential, were modulated by changing the total amount of surfactant mixture and the mixing ratio of eggPC and Tween 80 as surfactant mixture. The AR-loaded SLNs formulation was irradiated with a 60-W bulb to investigate the photostability. The extent of photodegradation was measured by high-performance liquid chromatography. The mean particle diameter and zeta potential of the smallest SLNs were 96 nm and -28 mV, respectively. The loading of AR in optimized SLNs formulations rather decelerated the degradation of AR, compared with AR solution dissolved in methanol. Our subsequent study showed that the co-loading of antioxidants greatly enhanced the stability of AR loaded in SLNs, compared with those loaded in SLNs without antioxidant. The photostability at 12 h of AR in SLNs was enhanced folds (43% approximately) higher than that in methanol solution (about 11%). Furthermore, the protecting effect of antioxidants was greatly dependent on the type of antioxidant. Taken together, AR could be effectively stabilized by being loaded in SLNs together with an antioxidant BHT-BHA.

Antioxidants↗

PubMed2006

Sensitive column-switching high-performance liquid chromatography method for determination of propiverine in human plasma.

A sensitive column-switching high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection was developed for the determination of propiverine in human plasma. Propiverine and internal standard, oxybutynin, were extracted from human plasma that had been made basic with 5N sodium hydroxide into methyl tert-butyl ether. The extracted plasma sample was injected onto the HPLC system consisting of a pretreatment column, a concentrating column, and an analytical column, which were connected with a six-port switching valve. The assay was linear in concentration ranges of 2-200 ng/ml for propiverine in human plasma. This method showed excellent sensitivity (a limit of detection of 0.5 ng/ml), good precision and accuracy. This method is suitable for bioequivalence studies following single dose in healthy volunteers.

Benzilates↗

PubMed2006

Polyethylenimine-based antisense oligodeoxynucleotides of IL-4 suppress the production of IL-4 in a murine model of airway inflammation.

BACKGROUND: Interleukin-4 (IL-4) plays a crucial role as an inflammatory mediator in allergic asthma via inducing Th2 inflammation and IgE synthesis. To develop an effective therapeutic agent which specifically inhibits production of IL-4, antisense oligodeoxynucleotides (AS-ODNs) against murine IL-4 mRNA were generated and complexed with polyethylenimine (PEI) to improve intracellular delivery. METHODS: AS-ODNs were generated against the translation initiation region of murine IL-4 mRNA, and complexed with linear PEI. In vitro efficacy of AS-ODNs/PEI complexes was tested by measuring IL-4 production in the D10.G4.1 cell line, and cytotoxicity was tested by XTT assay. Physicochemical properties of polyplexes were examined using atomic force microscopy (AFM) and DNase I protection assay. In vivo effects of IL-4 AS-ODNs/PEI complexes were tested in a murine model of airway inflammation. IL-4 concentrations in the bronchoalveolar lavage (BAL) fluid and circulating IgE levels were measured by ELISA, and histological analysis of lung tissues was performed. RESULTS: IL-4 AS-ODNs/PEI complexes were spheres with an average diameter of 98 nm and resistant to DNase I-mediated degradation. IL-4 AS-ODNs/PEI complexes showed up to 35% inhibition of IL-4 production in D10.G4.1 cells without causing any toxicity, while naked ODNs gave less than 1% reduction. Furthermore, IL-4 AS-ODNs/PEI complexes were effective in suppressing secretion of IL-4 (up to 30% reduction) in the BAL fluid in an ovalbumin-sensitized murine model of airway inflammation. Circulating IgE levels were decreased, and airway inflammation was alleviated by treatment with IL-4 AS-ODNs polyplexes. CONCLUSIONS: These data demonstrate that complexation of IL-4 AS-ODNs with PEI provides a potential therapeutic tool in controlling inflammation associated with allergic asthma, and further presents an opportunity to the development of clinical therapy based on combination of multiple AS-ODNs of cytokines and/or signaling effectors involved in Th2 inflammation and eosinophilia.

Animals↗

PubMed2006

Topical delivery of low-molecular-weight heparin with surface-charged flexible liposomes.

To increase topical delivery of low-molecular-weight heparin (LMWH), cationic, neutral, and anionic flexible liposomes (cFlexosome, nFlexosome, and aFlexosome) were prepared. The effects of surface charge of Flexosome on physicochemical properties and skin penetration of LMWH were also investigated. Among the different formulations of Flexosome, cFlexosome demonstrated three-times higher entrapment efficiency of LMWH, and better physicochemical stability than nFlexosome and aFlexosome. In vitro skin penetration and in vivo localization into the deeper skin layer of LMWH were significantly greater from cFlexosome compared to other formulations. Changes of skin surface charge after LMWH-cFlexosome application were investigated as a function of time. In the process of skin penetration, the Flexosomes act as drug carrier with the associated LMWH. Overall, macromolecular LMWH could be delivered deeply into the skin by topical application of cFlexosome for the treatment of superficial thrombosis, subcutaneous wounds, bruise, and burns.

Administration, Topical↗

PubMed2006

Polytetrafluoroethylene/polylactide-co-glycolide laminate containing dexamethasone allows delayed adjustable strabismus surgery in a rabbit model.

PURPOSE: To determine the usefulness of polytetrafluoroethylene/polylactide-co-glycolide (PTFE/PLGA) laminate containing dexamethasone in delayed adjustable strabismus surgery. METHODS: A prospective, masked-observer, controlled study was performed in rabbits. Fifty-two rabbit eyes were divided into three groups. After a recession of the superior rectus muscle (SRM), a PTFE/PLGA containing or not containing dexamethasone or balanced saline solution was applied beneath and over the SRM in the three treatment groups: the PTFE/PLGA-dexamethasone group (the P-D group), the PTFE group (the P group), and the control group (group C). Delayed adjustment was performed once on each SRM at 3 or 5 weeks after surgery by a masked observer. Adjustment lengths, the forces required, and degrees of adhesions were evaluated. RESULTS: In the control group, adjustment was possible in no eyes at 3 or 5 weeks after surgery. In group P, adjustment was possible in 6 of 10 eyes at 3 weeks after surgery and in 4 of 9 eyes at 5 weeks after surgery. In group P-D, adjustment was possible in 7 of 9 eyes at 3 and 5 weeks after surgery. CONCLUSIONS: PTFE/PLGA containing dexamethasone was found to allow delayed adjustment in most eyes for up to 5 weeks after surgery without instillation of anti-inflammatory agent.

Animals↗

PubMed2006

Effect of subconjunctivally injected, liposome-bound, low-molecular-weight heparin on the absorption rate of subconjunctival hemorrhage in rabbits.

PURPOSE: To investigate the effect of subconjunctival injection of liposome-bound, low-molecular-weight heparin (LMWH) on the absorption rate of subconjunctival hemorrhages. METHODS: Subconjunctival hemorrhages were induced in both eyes of 30 rabbits by the subconjunctival injection of 0.1 mL of autologous blood from auricular marginal veins. After 8 hours, randomized subconjunctival injections of one of three materials were made: 5 IU/mL liposome-bound LMWH (0.1 mL) in 18 eyes (group A), only liposomes (0.1 mL) in 14 eyes (group B), the free form of LMWH (5 IU/mL, 0.1 mL) in 14 eyes (group C), or no injection in 14 eyes (group D). Subconjunctival hemorrhages were photographed with a digital camera at 8, 24, 48, 72, 96, and 120 hours after induction of subconjunctival hemorrhages, sized with an image analyzer, and compared between groups. RESULTS: Subconjunctival hemorrhages were absorbed faster in group A (liposome-bound LMWH injected) than in with group B (liposome injected). Comparison of groups A and C (free LMWH injected) showed statistical differences in the absorption rates at 96 and 120 hours except at 24, 48, and 72 hours. The mean elapsed time for the complete resorption of subconjunctival hemorrhages was shortest in group A among four groups, whereas group B and the control showed no significant differences. The ocular and systemic absorption of LMWH were significantly lower after injection of the liposome-bound than the free form. CONCLUSIONS: The subconjunctival injection of liposome-bound LMWH appears to enhance subconjunctival hemorrhage absorption in rabbits.

Absorption↗

PubMed2005

A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption.

To enhance the dissolution and oral absorption of poorly water-soluble itraconazole, self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of itraconazole was formulated, and its physicochemical properties and pharmacokinetic parameters of itraconazole were evaluated. Among the surfactants and oils studied, Transcutol, Pluronic L64 and tocopherol acetate were chosen that showed the maximal solubility to itraconazole. The solubility of itraconazole was further improved by the addition of hydrochloric acid. Droplet size of itraconazole emulsion was kept constant both in simulated gastric fluid without pepsin (pH 1.2) and simulated intestinal fluid (pH 6.8) throughout 120-min incubation period. Itraconazole in the SEDDS rapidly dissolved in every dissolution medium whereas the Sporanox showed different dissolution patterns during the 120-min incubation according to the dissolution media. In fasted and fed normal diet group, AUC(0-->24 h) and the mean maximum plasma level (Cmax) of itraconazole after oral administration of SEDDS in rats were comparable to those of itraconazole after oral dose of Sporanox. However, in fed lipidic diet group, AUC and Cmax after oral administration of SEDDS in rats were 3.7- and 2.8-fold higher, respectively, compared with those of Sporanox. These results demonstrate that the SEDDS of itraconazole composed of Transcutol, Pluronic L64 and tocopherol acetate greatly enhanced the bioavailability of itraconazole after the dose, particularly not influenced by food intake or not. Thus, this system may provide a useful dosage form for oral water-insoluble drug without food effect.

Animals↗

PubMed2005

Trials of clear aceclofenac-loaded soft capsules with accelerated oral absorption in human subjects.

To develop an effective oral drug delivery system with accelerated absorption in human subjects for a poorly water-soluble acelofenac, five aceclofenac-loaded soft capsule preparations containing various ratios of different solubilizers were prepared and their dissolution tests were carried out. Among five preparations tested, a preparation with ethanolamine was selected as a formula of aceclofenac soft capsule (Korea United Pharm. Co. Ltd., Clanza S, since it was clear in appearance and showed the fastest dissolution rate due to the solubility-enhancing effect of aceclofenac. To evaluate and compare the pharmacokinetics of acelofenac-loaded soft capsules with the conventional aceclofenac tablets (Dae-Woong Pharm. Co. Ltd., Airtal) in human subjects; 14 normal healthy male volunteers (age 20-25 years old) were divided into two groups and a randomized 2 x 2 cross-over study was performed. Following oral administration of one tablet or capsule, each containing 100mg of aceclofenac, blood samples were collected at the predetermined time intervals and the concentration of aceclofenac in plasma was determined by HPLC method using UV detector. The AUC, Cmax, MRT, t1/2 and Kel of aceclofenac delivered from soft capsule were not significantly different from those from aceclofenac-loaded conventional tablet. However, soft capsule gave significantly higher initial concentration and significantly faster Tmax of aceclofenac than did conventional tablet, suggesting that the soft capsule with ethanolamine showed the faster absorption of aceclofenac in human subjects. Thus, the clear aceclofenac-loaded soft capsule with ethanolamine was a more effective oral dosage form with fast absorption for poorly water-soluble aceclofenac.

Absorption↗

PubMed2005

Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats.

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting point of various formulations composed of poloxamer 124 (P 124) and poloxamer 188 (P 188) were investigated. The dissolution and pharmacokinetic study of diclofenac sodium delivered by the poloxamer-based suppository were performed. Furthermore, the identification test in the rectum and morphology test of rectal tissues were carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous phases. Very small amounts of P 188 affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. Very small amounts of P 188 hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. The poloxamer-based suppository gave significantly higher initial plasma concentrations and faster T(max) of diclofenac sodium than did conventional PEG-based suppository, indicating that the drug from poloxamer-based suppository could be absorbed faster than that from PEG-based one in rats. It retained in the rectum for at least 4 h and could not irritate or damage the rectal tissues of rats. Thus, the poloxamer-based solid suppository with P 124 and P 188 was a mucoadhesive, safe and effective rectal dosage form for diclofenac sodium.

Adhesives↗

PubMed2005

Simultaneous determination of niflumic acid and its prodrug, talniflumate in human plasma by high performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of niflumic acid and its prodrug, talniflumate, in human plasma. Niflumic acid and talniflumate were eluted isocratically with methanol-water (73:27, v/v, adjusted to pH 3.5 by acetic acid) at a fl ow rate of 1 mL/min. Indomethacin was used as an internal standard. Signals were monitored by an UV detector at 288 nm. Retention times of indomethacin, niflumic acid and talniflumate were 5.9, 7.2 and 13.5 min, respectively. Calibration plots were linear over the range 50-5000 ng/mL for niflumic acid and 100-5000 ng/mL for talniflumate. The limits of quantitation were 50 ng/mL for niflumic acid and 100 ng/mL for talniflumate. The intra- and inter-day relative standard deviations (RSD) of niflumic acid and talniflumate were less than 10% and the accuracies were higher than 90%. This method is rapid, sensitive and reproducible for the determination of niflumic acid and talniflumate in human plasma.

Benzofurans↗

PubMed2005

Effect of edge activators on the formation and transfection efficiency of ultradeformable liposomes.

Highly deformable hydrophilic lipid vesicles have been studied for transdermal delivery of therapeutically active small molecules and proteins. Here, we report the effects of edge activators on the formation of ultradeformable liposomes (UL) and transdermal gene delivery. Sodium cholate, sodium deoxycholate, and Tween 80 were tested as edge activators. Of the edge activators, sodium cholate and sodium deoxycholate resulted in the smaller sizes of UL and more positive zeta potentials than did Tween 80. Moreover, sodium deoxycholate-based UL showed the highest positive zeta potentials, which might lead to the firmer binding with negatively charged DNA. Following topical application onto mice, DNA complexed with UL containing either sodium cholate or sodium deoxycholate showed substantial transdermal absorption. In contrast, DNA complexed with Tween 80-based UL did not show in vivo transdermal absorption. These data suggest that UL might be of use as a transdermal delivery system of plasmid DNA, and that the choice of edge activators may play an important role in the transdermal delivery of plasmid DNA via UL.

Administration, Topical↗

PubMed2005

Improved gene expression pattern using Epstein-Barr virus (EBV)-based plasmid and cationic emulsion.

To improve transgene expression of a non-viral gene delivery system, an Epstein-Barr virus (EBV)-based plasmid and cationic emulsion complex was prepared and evaluated. Cationic emulsion was formulated with castor oil, 3-N-(N',N'-dimethylaminoethane)-carbamoyl cholesterol (DC-Chol) and other co-emulsifiers. An EBV-based plasmid containing the two EBV components, origin of replication (oriP) and EBV nuclear antigen 1 (EBNA-1), was constructed. The physical characteristics of the emulsion and the emulsion/DNA complex were determined. After cells were transfected with cationic emulsion/EBV-based plasmid complex, transfection efficiency and expression pattern were evaluated using green fluorescent protein (GFP) as a reporter. The average particle size and zeta potential of the emulsion itself were 96 nm and + 17 mV, respectively. The emulsion showed stable size distribution up to at least one month. With an increase of emulsion to DNA ratio, zeta-potential increased from negative to positive and the particle size decreased to 200-300 nm. The complex was stable against DNase I digestion and showed comparable transfection efficiency with Lipofectin for several tested cell lines. An enhanced and prolonged gene expression was achieved using EBV-based plasmid and cationic emulsion complex. Combining physically stable emulsion with self-replicating EBV-based plasmid may confer more effective gene expression.

Carcinoma, Hepatocellular↗

PubMed2005

The use of chitosan as a condensing agent to enhance emulsion-mediated gene transfer.

Previously we have formulated a new cationic emulsion, composed of 3beta [N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol and dioleoylphosphatidyl ethanolamine, castor oil and Tween 80, and it efficiently delivered plasmid DNA into various cancer cells with low toxicity. Chitosan is a natural cationic polysaccharide and is able to form polyelectrolyte complexes with DNA, in which the DNA is condensed and protected against nuclease degradation. Based on these facts, chitosan was used as a condensing agent to enhance the transfection efficiency of cationic emulsion-mediated gene delivery vehicle. The particle size, zeta potential and transmission electron micrographs of DNA/emulsion complexes were observed before and after condensation by chitosan. In vitro transfection efficiency of naked or precondensed DNA/emulsion (pcDNA/E) complexes was investigated in human hepatoma cells (HepG2) using flow cytometer, confocal microscope and western blot. In addition, in vivo gene transfer was also evaluated as GFP mRNA expression by reverse transcriptase-polymerase chain reaction. The size of transfection complexes was reduced after the condensation of DNA by chitosan. Moreover, when the pcDNA/E complexes were administered into the mice, the GFP mRNA expression was prolonged in liver and lung until day 6. These results suggest that the use of chitosan enhance the in vitro transfection efficiency and extend in vivo gene transfer.

Animals↗

PubMed2005

Use of CP/MAS solid-state NMR for the characterization of solvate molecules within estradiol crystal forms.

To investigate the solvate molecules within estradiol crystal forms, four crystal forms of estradiol (EM, ET, EP and EC) were obtained by recrystallization from various organic solvents such as methanol, ethanol, isopropanol and acetone, and their physicochemical properties were characterized using XRD, TGA, DSC and solid-state NMR. The XRD patterns showed that the estradiol crystal forms were composed of high crystallinity and their degrees of crystallinity were nearly identical. The solvent phases and solvate molecules within the estradiol crystal forms were detected by thermal analysis and the solvate molecular structures were identified by further observation using solid-state NMR. Estradiol typically tends to crystallize in form of its hemihydrate by the solvate molecules from the mother solvents used for recrystallization. The residual solvent might be incorporated into the estradiol molecules to change the local chemical environment and cause the observed 13C CP/MAS NMR spectral changes. These results suggest that the thermal analysis and CP/MAS solid-state NMR spectroscopy could be useful at the dried solid state to characterize the solvate molecule within the recrystallized estradiols.

Crystallization↗

PubMed2005

Enhanced oral bioavailability of ibuprofen in rats by poloxamer gel using poloxamer 188 and menthol.

To improve the oral bioavailability of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the ibuprofen-loaded preparations composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed an abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.

Administration, Oral↗

PubMed2004

Narrow-bore high performance liquid chromatographic method for the determination of cetirizine in human plasma using column switching.

An improved column switching high performance liquid chromatographic (HPLC) method was developed for determination of cetirizine in human plasma. Plasma samples were prepared by liquid-liquid extraction using methylene chloride. The samples extracted were initially injected into a clean-up Capcell Pak MF C8 column and the peaks of cetirizine and internal standard were separated to an analytical C18 micro-column via column switching device. This analysis showed highly sensitive and selective results. Also, it was successfully applied to evaluate the pharmacokinetics of cetirizine in human volunteers after single oral administration.

Cetirizine↗