• Journal of the Korean Magnetic Resonance Society
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• v.2 no.1
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• pp.41-49
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• 1998

A linear undecapeptide, Substance P (SP) is involved in a wide variety of physiological processes such as pain, inflammation, salivation, and hypertension. Tertiary structure of SP in dodecylphosphocholine (DPC) micelles has been investigated by CD, NMR spectroscopy, and DGII calculation. CD spectrum of SP in the presence of 7.5 mM DPC micelles does not show any favorable secondary structure. The tertiary structure determined by NMR spectroscopy and DGII calculation shows that the Phe7-Phr8-Gly9-Leu10 region adopts a turn structure, while the N-terminal region is quite flexible. Both prolines in SP exist preferentially as the trans isoforms and the aromatic ring of Phe7 protrudes outward. Conformation of SP may be restrained by the contact of the Phe7 aromatic ring with the hydrophobic side chains of the DPC micelles and this interaction induces a turn structure. Structure of SP in aqueous solution in the presence of DPC micelles can represent a good model to study the conformation recognized by the receptor near neutral membrane.

• Bulletin of the Korean Chemical Society
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• v.12 no.4
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• pp.411-413
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• 1991

The effects of electrolyte on the critical micelle concentration (cmc) and bromide counterion binding in the micelles of cetylpyridinium bromide (CPB) have been investigated by UV spectroscopy and conductance measurements. Salts used in this study decreased cmc in the order $Cl^-\;<\;Br^-\;<\;NO3^-$ (which parallels the lyotropic series for the inorganic anions) and the effects on cmc followed the equation proposed by Shinoda: log cmc = A - B log (cmc + [NaX]). In the equation, constant B represents the counterion binding to the micelles at cmc and for the micelle of CPB at $25^{\circ}C$, B=80.76%. The association constant for the binding of counterions to long chain cations within micelles was also derived from the cmc values and counterion binding constant to the micelles.

• Bulletin of the Korean Chemical Society
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• v.35 no.10
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• pp.3030-3034
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• 2014

Bis-chloroethylnitrosourea (BCNU) is currently used as an anti-cancer drug for glioblastoma therapy. In this study, BCNU was loaded into the hydrophobic cores of R3V6 amphiphilic peptide micelles for efficient delivery into brain tumors. The scanning electron microscope (SEM) study showed that the BCNU-loaded R3V6 peptide micelles (R3V6-BCNU) formed spherical micelles. MTT assay showed that R3V6-BCNU more efficiently induced cell death in C6 glioblastoma cells than did BCNU. In the Annexin V assay, R3V6-BCNU more efficiently induced apoptosis than did BCNU alone. Furthermore, the results showed that R3V6 was not toxic to cells. The positive charges of the R3V6 peptide micelles may facilitate the interaction between R3V6-BCNU and the cellular membrane, resulting in an increase in cellular uptake of BCNU. In vivo evaluation with an intracranial glioblastoma rat model showed that R3V6-BCNU more effectively reduced tumor size than BCNU alone. The results suggest that R3V6 peptide micelles may be an efficient carrier of BCNU for glioblastoma therapy.

• Archives of Pharmacal Research
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• v.23 no.4
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• pp.367-373
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• 2000

Cholic acid, conjugated with amine-terminated poly(W-isopropylacrylamide) (abbreviated as CA/ATPNIPAAm), was synthesized by a N, N'-dicyclohexyl carbodiimide (DCC)-mediated coupling reaction. Self-assembled CA/ATPNIPAAm micelles were prepared by a diafiltration method in aqueous media. The CA/ATPNIPAAm micelles exhibited a lower critical solution temperature (LCST) at $31.5^{\circ}C$. Micelle sizes measured by photon correlation spectroscopy (PCS) were approximately 31.6 $\times$$\times$ 5.8 nm. The CA/ATPNIPAAm micelles were spherical and their thermal size transition was observed by transmission electron microscope (TEM). A fluorescence probe technique was used for determining the micelle formation behavior of CA/ATPNIPAAm in aqueous solutions using Pyrene as a hydrophobic Probe. The critical micelle concentration (CMC) was evaluated as $8.9{\times}0^{-2}$ g/L. A drug release study was performed using indomethacin (IN) as a hydrophobic model drug. The release kinetics of IN from the CA/ATPNIPAAm micelles revealed a thermo-sensitivity by the unique character of poly(N-isopropylacrylamide) i.e. the release rate was higher at $25^{\circ}C$ than at $37^{\circ}C$.

• Bulletin of the Korean Chemical Society
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• v.14 no.5
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• pp.599-602
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• 1993

Micellization process of dodecyltrimethylammonium bromide (DTAB) was studied by using the aromatic probe (benzene) which dissolved in aqueous DTAB solutions. Proton NMR chemical shift measurements of DTAB and DTAB-benzene system showed that benzene molecules solubilized near the micelle-water interface and that the solubilization sites within the micelles are different as the DTAB concentration is passing through 32.0 mM (hereafter we refer this concentration as the second CMC). The change of solubilization sites is also confirmed by abrupt changes of the chemical shifts and relaxation rates of benzene protons in DATB-benzene system at this concentration. It was revealed from the electrical conductivity and viscosity measurements that the solubilization of benzene caused the DTAB micelles to swell out and that the micelles prepared after the second CMC had a greater swelling effect than those prepared before the second CMC. The transition point which reflects the saturation of benzene molecules on the solubilization sites of micelles was observed at one benzene/micellized DTAB mole ratio from the electrical conductivity measurements. Along the different concentration of DTAB solution, this transition point is appeared clearly after the second CMC. From these results it is suggested that the shapes and/or sizes of DTAB micelles of the spherical micelle region prepared after the second CMC are different from those prepared before the second CMC.

• Journal of the Korean Magnetic Resonance Society
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• v.11 no.2
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• pp.85-94
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• 2007

Vanilloid receptor I [transient receptor potential vanilloid subfamily member 1 (TRPV1), also known as VR1] is a non-selective cationic channel activated by noxious heat, vanilloids, and acid, thereby causing pain. VR1 possesses six transmembrane domain and N-and C-terminus cytosolic domains, and appears to be a homotetramer. We studied the structural properties of Cterminus of VR1 (VR1C) using CD and NMR spectroscopy. DPC micelles, with a zwitterionic surface, and SDS micelles, with a negatively charged surface, were used as a membrane mimetic model system. Both SDS and DPC micelles could increase the stability of helical structures and/or reduce the aggregation form of the VR1C. However, the structural changing mode of the VR1C induced by the SDS and DPC micelles was different. The changes according to the various pHs were also different in two micelles conditions. Because the net charges of the SDS and DPC micelles are negative and neutral, respectively, we anticipate that this difference might affect the structure of the VR1C by electrostatic interaction between the surface of the VR1C and phospholipids of the detergent micelles. Based on these similarity and dissimilarity of changing aspects of the VR1C, it is supposed that the VR1C probably has the real pI value near the pH 7. Generally, mild extracellular acidic pH ($6.5{\sim}6.8$) potentiates VRI channel activation by noxious heat and vanilloids, whereas acidic conditions directly activate the channel. The channel activation of the VRI might be related to the structural change of VR1C caused by pH (electrostatic interactions), especially near the pH 7. By measuring the $^1-^{15}N$ TROSY spectra of the VR1C, we could get more resolved and dispersed spectra at the low pH and/or detergent micelles conditions. We will try to do further NMR experiments in low pH with micelles conditions in order to get more information about the structure of VR1C.

• Polymer(Korea)
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• v.36 no.4
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• pp.420-426
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• 2012

In this study, we prepared polymer micelles containing quercetin and rutin, known as antioxidants, using poly(${\varepsilon}$-caprolactone)-b-poly(ethylene glycol), and evaluated in vitro skin permeation of the active materials. Quercetin and rutin loaded micelles were characterized by DSC (differential scanning calorimetry), HPLC (high performance liquid chromatography) and DLS (dynamic light scattering) measurements. The particle size of the polymer micelles increased in a concentration dependent manner (0.5~2.0% PCL-b-PEG). The Zeta potential of quercetin and rutin loaded micelles remained constant. To evaluate the skin penetration of PCL-b-PEG micelles, Franz diffusion cell experiment was performed. The aqueous solutions of quercetin and rutin were used as the control groups. Quercetin and rutin loaded PCL-b-PEG micelles showed more efficient skin permeation than the control groups. Safety assessment (patch test) of quercetin and rutin loaded PCL-b-PEG micelles on skin was performed to test application possibility of the polymer micelles to cosmetics. Any adverse symptoms were not observed.

• Bulletin of the Korean Chemical Society
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• v.32 no.7
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• pp.2187-2192
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• 2011

Hydrogen peroxide plays a key role as a second messenger in the normal cellular signaling but its overproduction has been implicated in various life-threatening diseases. Peroxalate chemiluminescence is the light emission from a three component reaction between peroxalate, hydrogen peroxide and fluorophores. It has proven great potential as a methodology to detect hydrogen peroxide in physiological environments because of its excellent sensitivity and specificity to hydrogen peroxide. We developed chemiluminescent micelles composed of amphiphilic polymers, peroxalate and fluorescent dyes to detect hydrogen peroxide at physiological concentrations. In this work, we studied the relationship between the chemiluminescence reactivity and stability of peroxalate by varying the substitutes on the aryl rings of peroxalate. Alkyl substitutes on the aryl ring of peroxalate increased the stability against water hydrolysis, but diminished the reactivity to hydrogen peroxide. Chemiluminescent micelles encapsulating diphenyl peroxalate showed significantly higher chemiluminescence intensity than the counterpart encapsulating dimethylphenyl or dipropylphenyl peroxalate. Diphenyl peroxalate-encapsulated micelles could detect hydrogen peroxide generated from macrophage cells stimulated by lipopolysaccharide (LPS) and image hydrogen peroxide generated during LPS-induced inflammatory responses in a mouse.

• Journal of Life Science
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• v.20 no.11
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• pp.1611-1616
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• 2010

The purpose of this research was to determine the effect of surfactant micelles on lipid oxidation in W/O/W multiple emulsions. The content of ferric irons and hydroperoxide in the continuous phase in W/O/W multiple emulsions was measured as a function of Brij micelle. The concentration of ferric iron and hydroperoxide in the continuous phase increased with increased storage time (1~6 days). Lipid oxidation rates, as determined by the formation of lipid hydroperoxides, TBARs and headspace hexanal, in the W/O/W multiple emulsions containing ferric iron decreased when 3% surfactant micelles were exceeded. These results indicate that excess surfactant micelles could alter the physical location and prooxidant activity of iron in W/O/W multiple emulsions.

• Archives of Pharmacal Research
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• v.26 no.2
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• pp.173-181
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• 2003

A polymeric micelle drug delivery system was developed to enhance the solubility of poorly-water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The block copolymers consisting of poly(D,L-lactide) (PLA) as the hydrophobic segment and methoxy poly(ethylene glycol) (mPEG) as the hydrophilic segment were synthesized and characterized by NMR, DSC and MALDI-TOF mass spectroscopy. The size of the polymeric micelles measured by dynamic light scattering showed a narrow monodisperse size distribution with the average diameter less than 50 nm. The MW of mPEG-PLA, 3000 (MW of mPEG, 2 K; MW of PLA, 1K), and the presence of hydrophilic and hydrophobic segments on the polymeric micelles were confirmed by MALDI-TOF mass spectroscopy and NMR, respectively. Polymeric micelle solutions of DDB were prepared by three different methods, i.e. the matrix method, emulsion method and dialysis method. In the matrix method, DDB solubility was reached to 13.29 mg/mL. The mPEG-PLA 2K-1K micelle system was compared with the poloxamer 407 micelle system for their critical micelle concentration, micelle size, solubilizing capacity, stability in dilution and physical state. DDB loaded-polymeric micelles prepared by the matrix method showed a significantly increased aqueous solubility (＞5000 fold over intrinsic solubility) and were found to be superior to the poloxamer 407 micelles as a drug carrier.