• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.93-98
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• 1999

Semi-solid poly(ortho esters) (POE) were prepared to provide bioerodible carriers for sustained drug delivery systems of nifedipine in the treatment of cardiovascular disease. As the POE has viscous behavior at room temperature, a significant advantage of this polymer is that it can be injected without any surgical intervention. The POE was synthesized by a transesterification reaction between 1,2,6-hexanetriol and trimethyl orthoacetate and the nifedipine release from POE was studied in vitro. The release rate of nifedipine decreased with increasing the amount of nifedipine and the diethanolamine dispersed in the polymer. But the excess amounts, above 3%, of diethanolamine retarded the release of nifedipine. In vivo biocompatibility studies were carried out in rats with nifedipine loaded POE. Histopathological analysis showed that nifedipine loaded POE implants were well-tolerated by rats when used subcutaneously. In case of the rats implanted POE containing diethanolamine, tissue necrosis and inflammation were occured. Pharmacokinetic studies of nifedipine loaded POE implants were carried out in rabbits. In all cases, plasma concentrations of nifedipine were maintained over 15 ng/ml for at least 360 hours and biological half $life(t_{1/2})$ and mean residence time(MRT) were increased by addition of diethanolamine.

• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.85-91
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• 2009

Microcrystallized cellulose xanthate-metal-oxytetracycline complexes (MCX-metal-OTC) were prepared and evaluated as a controlled release system for the antibiotics. Microcrystallized cellulose (MC) was chemically modified to xanthated microcrystallized cellulose (MCX). One-bath method, where MCX was reacted with OTC-metal complexes, afforded greater amount of OTC bound to the polymeric matrix than did two-bath method, where MCX-metal complexes were treated with OTC. The OTC release from MCX-metal-OTC was greatly sustained compared with that from a mixture of MC/metal/OTC. Furthermore, MCX-metal-OTC manifested antibacterial activity, which lasted for 11-18 days. These results suggest that MCX-metal-OTC is a polymeric antibiotics with prolonged antibacterial activity.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.73-80
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• 2005

The effect of capsaicin on apoptotic cell death was investigated in HepG2 human hepatoma cells. Capsaicin induced apoptosis in time- and dose-dependent manners. Capsaicin induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration, and BAPTA, an intracellular $Ca^{2+}$ chelator, significantly inhibited capsaicin-induced apoptosis. The capsaicin-induced increase in the intracellular $Ca^{2+}$ and apoptosis were not significantly affected by the extracellular $Ca^{2+}$ chelation with EGTA, whereas blockers of intracellular $Ca^{2+}$ release (dantrolene) and phospholipase C inhibitors, U-73122 and manoalide, profoundly reduced the capsaicin effects. Interestingly, treatment with the vanilloid receptor antagonist, capsazepine, did not inhibit either the increased capsaicin-induced $Ca^{2+}$ or apoptosis. Collectively, these results suggest that the capsaicin-induced apoptosis in the HepG2 cells may result from the activation of a PLC-dependent intracellular $Ca^{2+}$ release pathway, and it is further suggested that capsaicin may be valuable for the therapeutic intervention of human hepatomas.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.269-273
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• 2009

The objective of this investigation was to develop a gastro-retentive(GR) dosage form of gabapentin and was to evaluate of its dissolution characteristics. GR tablet consists of expandable core tablet matrix and semi-permeable membrane coating. Poloxamer 407 and sodium bicarbonate were used to prepare the core matrix. Polyvinly acetate dispersion (Kollicoat $SR30D^{(R)}$) and polyvinyl alcohol-polyethylene glycol copolymer ((Kollicoat $IR^{(R)}$)) were employed to form the semi-permeable membrane. The GR tablets significantly expanded up to fivefold in simulated gastrointestinal fluids with no apparent damage of the coating membrane over 12 hours. Also, the swelling rate was controllable with the amount of sodium bicarbonate. The drug release was observed to be substantially sustained based on coating level. The release rate of gabapentin from the GR tablet was gradually slowed down as the coasting amount was increased. The gabapentin GR tablet with 8% coating level showed a pseudo-zero order release kinetics over 12 hours. These results suggest that this swellable GR tablet system having semi-permeable membrane coating can be applicable for hydrophilic drug substances like gabapentin.

• The Korean Journal of Food And Nutrition
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• v.31 no.2
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• pp.308-312
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• 2018

Even though chlorine dioxide ($ClO_2$) is utilized in a pre-treatment due to its effective sterilizing activity for microorganisms and its safety for food, it has a limitation in maintaining freshness of the food product. In this study, a low-concentration $ClO_2$ gas was produced in a packaging form of air-permeable gel pack so that it could be released continuously over several days. The amount of $ClO_2$ gas emission and microbial inactivation effect against foodborne pathogens were measured during the release of $ClO_2$ gas. As a result of measuring the change of color in order to confirm whether the chlorine dioxide gas was eluted in the form of a sustained release, the yellowness was significantly higher at higher gel pack concentration and higher value during storage periods. The slow-released $ClO_2$ gel-pack showed clear inactivation effect against Escherichia coli and Staphylococcus aureus with 99.9% inactivation efficiency. As a result of measuring the sterilization effect of Listeria monocytogenes by the concentration of chlorine dioxide gas, the sterilization effect was increased as the concentration was increased. Therefore, the slow-released $ClO_2$ gel-pack is feasible to apply for industry usages.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1245-1252
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• 2004

Although ascorbate (vitamin C) has been shown to have anti-cancer actions, its effect on human hepatoma cells has not yet been investigated, and thus, the exact mechanism of this action is not fully understood. In this study, the mechanism by which ascorbate induces apoptosis using HepG2 human hepatoblastoma cells is investigated. Ascorbate induced apoptotic cell death in a dose-dependent manner in the cells, was assessed through flow cytometric analysis. Contrary to expectation, ascorbate did not alter the cellular redox status, and treatment with antioxidants (N-acetyl cysteine and N,N-diphenyl-p-phenylenediamine) had no influence on the ascorbate-induced apoptosis. However, ascorbate induced a rapid and sustained increase in intracellular $Ca^{2+}$ concentration. EGTA, an extracellular $Ca^{2+}$ chelator did not significantly alter the ascorbate-induced intracellular $Ca^{2+}$ increase and apoptosis, whereas dantrolene, an intracellular $Ca^{2+}$ release blocker, completely blocked these actions of ascorbate. In addition, phospholipase C (PLC) inhibitors (U-73122 and manoalide) significantly suppressed the intracellular $Ca^{2+}$ release and apoptosis induced by ascorbate. Collectively, these results suggest that ascorbate induced apoptosis without changes in the cellular redox status in HepG2 cells, and that the PLC-coupled intracellular $Ca^{2+}$ release mechanism may mediate ascorbate-induced apoptosis.

• Journal of Pharmaceutical Investigation
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• v.41 no.3
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• pp.185-190
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• 2011

The purpose of this study was to evaluate the phagocytic uptake of surface modified PLGA microspheres containing ovalbumin (OVA) into dendritic cell. In order to find the most suitable formulation for targeted delivery to antigen presenting cells (APC), OVA was encapsulated by a double emulsion solvent evaporation method with three PLGA microspheres (PLGA 50:50, PLGA 75:25 and PLGA 85:15) and two surface modified microspheres by chitosan and sodium dodecyl sulfate (SDS). Physicochemical properties were evaluated in terms of size, zeta potential, encapsulation efficiency, different scanning calorimeter (DSC), x-ray diffraction, morphology, and OVA release test from microspheres. Phagocytic activity was estimated using dendritic cells and analyzed by fluorescence activated cell sorter (FACS). The result showed that zeta potential of PLGA particles was changed to positive by the chitosan modification. The release profile of chitosan modified PLGA microspheres exhibited sustained release after initial burst. The chitosan modified microspheres had higher phagocytic uptake than the other microspheres. Such physicochemical properties and phagocytic uptake studies lead us to conclude that chitosan modified microspheres is more suitable formulation for the targeted delivery of antigens to APC compared with the other microspheres.

• Macromolecular Research
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• v.12 no.3
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• pp.269-275
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• 2004

To graft N-isopropylacrylamide (NIPAAm) onto alginate, varying dosages of ${\gamma}$-rays were irradiated onto alginate films in deionized water and methanol media, which are non-solvents of alginate. We investigated the hydrogels graft ratio, mechanical strength, swelling kinetics and ratio, and behavior with respect to drug release. The graft yield of NIPAAm increased upon increasing the irradiation dose. The use of the aqueous solution increased the graft yield relative to that obtained in methanol. The mechanical strength of the grafted hydrogels increased after grafting with NIPAAm. In a study of the swelling kinetics, we found that all hydrogels reached an equilibrium swollen state within 3 h. The equilibrium swelling ratio of the hydrogels decreased upon increasing the irradiation dose. The swelling ratio of the hydrogels decreased dramatically between 30 and 35$^{\circ}C$ because phase separation of NIPAAm occurred at 32$^{\circ}C$. The swelling process, with respect to the temperature change, was repeatable. An NIPAAm-grafted alginate containing a drug sustained its release rate until 3 h after an initial high drug release caused by a burst effect.

• Journal of the Korean Society of Combustion
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• v.19 no.1
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• pp.29-38
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• 2014

This paper described an experimental investigations of combustion instability mode in a lean premixed dual swirl combustor for micro-gasturbine system. When such the instability occurs, a strong coupling between pressure oscillations and unsteady heat release excites a self-sustained acoustic wave which results in a loud, annoyed sound and may also lead a structural damage to the combustion chamber. The detailed period of flame behavior and heat release in combustion instability mode have been examined with high speed OH and CH-PLIF system and $CH^*$ chemiluminescence measurement, flame tomography with operated at 10 kHz and 6 kHz each. Experiment results suggest that unstable flame behavior has a specific frequency with 200 Hz and this frequency is accords with about 1/2 sub-harmonic of combustor resonance frequency, not fundamental frequency. This is very interesting phenomenon that have not reported yet from other previous works. Therefore, when a thermo-acoustic instability with Rayleigh criterion occurs, the fact that the period of heat release and flame behavior are different each other was proposed for the first time through this work.

• Archives of Pharmacal Research
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• v.19 no.4
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• pp.280-285
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• 1996

The sustained release dosage form which delivers melatonin (MT) in a circadian fashion over 8 h is of clinical value for those who have disordered circadian rhythms because of its short halflife. The purpose of this study was to evaluate the gelling properties and release characteristics of alginate beads varying multivalent cationic species $(Al^{+++}, \; Ba^{++}, \; Ca^{++}, \; Mg^{++}, \; Fe^{+++}, \; Zn^{++})$. The surface morphologies of Ca- and Ba-alginate beads were also studied using scanning electron microscope (SEM). MT, an indole amide pineal hormone was used as a model drug. The $Ca^{++}, \; Ba^{++}, \; Zn^{++}, \; Al^{++}\; and\; Fe^{+++}\; ions\; except\; Mg^{++}$ induced gelling of sodium alginate. The strength of multivalent cationic alginate beads was as follows: $Al^{+++}\llFe^{+++} the induced hydrogel beads were very fragile and less spherical. Fe-alginate beads were also fragile but stronger compared to Al-alginate beads. Ba-alginate beads had a similar gelling strength but was less spherical when compared to Ca-alginate beads. Zn-alginate beads were weaker than Ca- and Ba-alginate beads. Very crude and rough crystals of Ba- and Ca-alginate beads at higher magnifications were observed. However, the type and shape of rough crystals of Ba- and Ca-alginate beads were quite different. No significant differences in release profiles from MT-loaded multivalent cationic alginate beads were observed in the gastric fluid. Most drugs were continuously released upto 80% for 5 h, mainly governed by the passive diffusion without swelling and disintegrating the alginate beads. In the intestinal fluid, there was a significant difference iq the release profiles of MT-loaded multivalent cationic alginate beads. The release rate of Ca-alginate beads was faster when compared to other multivalent cationic alginate beads and was completed for 3 h. Ba-alginate beads had a very long lag time (7 h) and then rapidly released thereafter. MT was continuously released from Feand Zn-alginate beads with initial burstout release. It is assumed that the different release rofiles of multivalent cationic alginate beads resulted from forces of swelling and disintegration of alginate beads in addition to passive diffusion, depending on types of multivalent ions, gelling strength and drug solubility. It was estimated that 0.2M $CaCl_2$ concentration was optimal in terms of trapping efficiency of MT and gelling strength of Ca-alginate beads. In the gastric fluid, Ca-alginate beads gelled at 0.2 M $CaCl_2$ concentration had higher bead strength, resulting in the most retarded release when compared to other concentrations. In the intestinal fluid, the decreased release of Ca-alginate beads prepared at 0.2 M $CaCl_2$ concentration was also observed. However, release profiles of Ca-alginate beads were quite similar regardless of $CaCl_2$ concentration. Either too low or high $CaCl_2$ concentrations may not be useful for gelling and curing of alginate beads. Optimal $CaCl_2$ concentrations must be decided in terms of trapping efficiency and release and profiles of drug followed by curing time and gelling strength of alginate beads.