• Polymer(Korea)
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• v.30 no.6
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• pp.464-470
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• 2006

Diblock copolymers consisting of methoxy Poly (ethylene glycol) (MPEG) and poly (${\epsilon}-ca$ prolactone) (PCL), poly(${\delta}-valerolactone$) (PVL), poly(L-lactide) (PLLA), or poly(L-lactide-co-glycolide) (PLGA) were prepared to compare the characterization of diblock copolymers as a drug carrier. MPEG-PCL, MPEG-PVL, MPEG-PLLA, and MPEG-PLGA diblock copolymers were synthesized by the ring-opening polymerization of ${\epsilon}$-caprolactone or ${\delta}$-valerolactone in the presence of $HCl{\cdot}Et_2O$ as a monomer activator at room temperature and by the ring-opening polymerization of L-lactide or a mixture of L-lactide and glycolide in the presence of stannous octoate at $130^{\circ}C$, respectively. The synthesized diblock copolymers were characterized with $^1H-NMR$, GPC, DSC, and XRD. The micellar characterization of MPEG-polyester diblock copolymers in an aqueous phase was carried out by using NMR, dynamic light scattering, AFM, and fluorescence techniques. Most micelles exhibited a spherical shape in AFM. Thus, ore confirmed that the micelles formed with MPEG-polyester diblock copolymers have possibility as a potential hydrophobic drug delivery vehicle because a hydrophobic drug could be preferentially distributed in the micelle core.

• Journal of the Korean Ceramic Society
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• v.35 no.6
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• pp.594-602
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• 1998

Titanium hydroxide (TiO({{{{ {OH }_{2 } }})) fine particles were produced by the reverse micelle technique. For the formation of titanium hydroxide (TiO({{{{ {OH }_{2 } }})) particles with the technique reversed micellar solution was prepared by solubilizing water into organic solvent (isooctane) with a surfactant and titanium alkoxide (tetraisopropyl orthotitanate) diluted with isopropyl alcohol was added to the reversed micellar solution. The hdrolyzed species (TiO({{{{ {OH }_{2 } }})) was formed by the hydrolysis of titanium alkoxide and titanium dioxide is then formed by the condensation of the hydrolyzed species. There are several process variables such as surfactants concentration of surface cosurfactant hydrolysis temperature and pH. In this work the ef-fects of process variables on paticle shapes particle size distribution and paticle agglomeration were bi-nodal for an anionic surfactant(AOT) in the whole range of temperature pH and surfactant concentration of this experiment. The addition of ethanol as a cosurfactant resulted in narrow particle size distribution of the experiment. The additiono of ethanol as a cosurfactant resulted in narrow particle size distribution and 0.12${\mu}{\textrm}{m}$ of smaller average particle diameter. FT-IR spectrum of particles shows the absorption peak of Ti-OH bonding and Ti-O bonding. An exothermic peak around 41$0^{\circ}C$ in TGA-DTA curve shows that crys- tallized anatase phase appears and completely transits to anatase around 45$0^{\circ}C$.

• KSBB Journal
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• v.15 no.6
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• pp.664-669
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• 2000

Micellar aggregates are known to be useful for the selective isolation of biologically active materials such as amino acids, proteins, and enzymes from crude mixtures sparsely dispersed in water. In this study, the effects of pH, salt type and its concentration on the solubilization of $\alpha$-chymotrypsin into the organic micellar phase, which consisted of AOT (sodium 야(2-ethylhexy)sulfosuccinate) and iso-octane, were comprehensively examined. It was found that maximum extraction efficiency was attained at a pH below the isoelectric point of $\alpha$-chymotrypsin; at pH=5.0 for NaCl and KCl, and at pH=7.0 for $CaCl_2$and $MgCl_2$. In order to avoid complications stemming from the precipitationof protein at low pH interfaces, the protein concentrations in the organic and aqueous phases were directly measured. The size of the micelle water pool was estimated by measuring the molar ratio of the surfactant to the water, W(sub)o. The resulting values of W(sub)o were nearly constant at 30 and 19 for NaCl and KCl, respectively, and were independent of pH. The addition of 1:2 salts like $MgCl_2$and $CaCl_2$ led to much lower, but a constant value of, W(sub)o than the 1:1 salts.

• Journal of the Korean Chemical Society
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• v.33 no.1
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• pp.3-10
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• 1989

In order to obtain a clue in understanding enzymatic hydrolysis in which the His-Cys moieties of papain protease is involved, we prepared cationic peptide-sufactants bearing histidyl, cysteinyl, and both histydyl and cysteinyl residues. Their catalytic efficiency toward the hydrolysis of PNPL were investigated in comicellar phases formed with $N^{+}C_{2}CysC_{12}$, $N^{+}C_{2}HisC_{12}$, $N^{+}C_{2}HisCysC_{12}$ increased markedly in the same order compared with that of $N^{+}C_{2}AlaC_{12}$. The markedly increased catalytic effects are attributed to the imidazole groups of $N^{+}C_{2}HisC_{12}$ and the thiol groups of $N^{+}C_{2}CysC_{12}$, and the large catalytic efficiency of $N^{+}C_{2}HisCysC_{12}$, is considered due to the interaction of the imidazole and the thiol groups. In order to investigate catalytic activities, rate constants for the functional groups, km* and dissociation constants, pKa have been determined. The results showed that $k^{\ast}_m$ and pKa of the imidazole groups were $7.91{\times}10^{-4}S^{-1}$ and 6.49, and those of the thiol groups were $6.00{\times}10^{-4}S^{-1}$ and 10.50. The catalytic effects of comicellar systems on the hydrolysis of p-nitrophenyl esters has increased according to the increasing size of the alkyl carbon number. Therefore, the catalytic effects have been increasing by the interaction of micellar hydrophobic parts and substrates as well as action of the functional groups.

• Archives of Pharmacal Research
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• v.24 no.6
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• pp.584-589
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• 2001

Isopropryl 2-(1-3-dithiethane-2-ylidene)-2 [N-(4-methyl-thiazole-2-yl) carbamoyl] acetate (YH439) is currently under phase ll clinical trials by the Yuhan Research Center for use as a hepatoprotective agent. Unfortunately, the oral bioavailbility of YH439, which is sparingly soluble in water (i.e., $0.3{\;}\mu\textrm{g}/ml{\;}or{\;}0.91{$\mu}M$ at room temperature), reportedly, is negligibleregardless of the dose administered to rats in the 10-300 mg/kg range. The bioavailability of the compound increased up to 24%, when administered in the form of a micellar solution ($700{\;}\mu\textrm{g}/ml$or 2.1 mM for YH439) at a dose of 10 mg/kg, suggesting that its limited solubility is associated with its negligible bioavailability. In order to obtain additional informmation concerning the bioavailability of YH439, the mechanism(s) involved in gastrointestinal (Gl) absorption were investigated in the present study. For this purpose, the transport of YH430 across a Caco-2 cell monolayer was measured in a $Transwell^{\circledR}$. A permeability of $4.07{\times}10^{-5}{\;}cm/s$ was obtained for the absorptive (i.e., apical to basolateral direction) transport of $0.42{\mu}M$ YH439, implicating that the in vivo Cl absorption is nearly complete. The absorptive transport exhibited a slight concentration-dependency with an intrinsic clearance ($CL_{i}$) of $0.38{\mu}L/{\textrm{cm}^2}/sec$, which accounted for 28.1% of the total intrinsic clearance (i.e., $CL_i$ plus the intrinsic clearance for the linear component) of the transport. Thus, saturation of the absorption process appears to be a minor factor in limiting the bioavailability of the compound. The apparent permeability of YH439 from the basolateral to the apical direction (i.e., efflux, $6.67{\times}10^{-5}{\;}cm/s$) was comparable to that for absorptive transport, but, interestingly, a more distinct concentration-dependency was observed for this transport. However, the efflux does not appear to influence the bioavailability of the compound, as evidenced by the sufficiently high permeability in the absorption direction. Rather, a reportedly extensive first-pass hepatic metabolism appears to be a principal factor in limiting the bioavailability. In this respect, reducing the first-pass metabolism by some means would lead to a higher bioavailability of the compound. Thus, elevation of the absorption rate of YH439 becomes a necessity. From a practical point of view, increasing the concentration of YH439 in the Cl fluid appears to be a feasible way to increase the absorption rate, because the compound is primarily absorbed via a linear mechanism. In summary, the solubilization of YH439, as previously demonstrated for a micellar solution of the compound, appears to be a practical way to increase the oral bioavailability of YH439.

• Journal of Photoscience
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• v.2 no.2
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• pp.89-93
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• 1995

Solvatochromic effects and hydrogen bonding interactions of 4-hydroxy-4'-nitrostilbene(NSOH) were investigated. Electronic transition energies of NSOH have good correlation with Taft's $\pi$$^*$. The hydrogen bonding interactions can be accounted by analysis with equation of $\Delta$E= $\Delta$E$_0$ + s($\pi$$^*$ + d$\delta$) + a$\alpha$ + b$\beta$. From UV-visible absorption maximum energies, $\Delta$E = 81.2 kcal/mole - 6.66($\pi$$^*$ - 0.20$\delta$) - 0.66$\alpha$ - 1.93$\beta$ (corr.=0.970) was obtained, and from fluorescence intensity maximum energies, $\Delta$E= 70.07 kcal/mole - 21.6($\pi$$^*$ - 0.11d) - 1.74$\alpha$ - 2.73$\beta$ (corr.=0.947) was obtained. The micropolarity estimated at the solubilization sites is close to the polarity of water. The apparent Taft's $\pi$$^*$ values of solubilization sites are close to 1. Howcver, the solubilization sites for the fluorescent NSOH is rather nonpolar. Both NSOH and NSO$^-$ can be solubilized in CTAB and CTAC micelles and NSOH is the only species that can be solubilized in SDS and Brij-35 micelles.

• Bulletin of the Korean Chemical Society
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• v.29 no.8
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• pp.1539-1544
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• 2008

A polymeric micelle, based on the poly(benzyl-L-histidine)-b-poly(ethylene glycol) (polyBz-His-b-PEG) diblock copolymer, was designed as a tumor-specific targeting carrier. The micelles (particle size: 67-80 nm, critical micelle concentration (CMC); 2-3 $\mu$g/mL) were formed from the diafilteration method at pH 7.4, as a result of self-assembly of the polyBz-His block at the core and PEG block on the shell. Removing benzyl (Bz) group from polyBz-His block provided pH-sensitivity of the micellar core; the micelles were physically destabilized in the pH range of pH 7.4-5.5, depending on the content of the His group free from Bz group. The ionization of His group at a slightly acidic pH promoted the deformation of the interior core. These pHdependent physical changes of the micelles provide the mechanism for pH-triggering anticancer drug (e.g., doxorubicin: DOX) release from the micelle in response to the tumor’s extracellular pH range (pH 7.2-6.5).

• Journal of the Korean Chemical Society
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• v.20 no.3
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• pp.193-197
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• 1976

The ultrasonic absorption has been measured in aqueous solution of dodecyl pyridinium chloride (DPC) at $20^{\circ}C$ over the frequency range of 0.1${\sim}$90 Mc.The excess absorption was observed only in solutions in which the concentration was higher than the critical micellar concentration(cmc). The mechanism for this feature was attributed to the reaction $M_2\;{\rightleftharpoons}\;M_1\;＋\;1.2Cl^-$ Where $M_2$ and $M_1$ and M1 are two types of micelle. The rate constants of the forward and the reverse reactions were $6.6{\times}10^5 sec^{-1}\;and\;2.7{\times}10^11sec^{-1}mol^{-1.2}$respectively. Some kinetic charateristics including the free energy, enthalpy and entropy were calculated.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.201-201
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• 1994

항암 및 면역조절작용을 가지고 있으며 그자체가 서방성 prodrug으로서 약효를 나타낼것으로 기대되는 ara-C와 etherphospholipid의 conjugate인 ara-CDP-DL-PCA.2Na의 실험동물(rat)에서의 체내동태를 HPLC 정량법으로 시행 하였다. Ara-CDP-DL-PCA.2Na의 정맥내 투여(20mg/300g)의 경우 혈장중 반감기는 분포상에 있어서는 평균 20min, 소실상 에서는 4.42hr이었다. 분포 용적은 0.1635Lㆍkg$^{-1}$이었고, 전신 clearance 는 25.63ml.$hr^{-1}$.kg$^{-1}$이었다. 한편 AUC는 2601$\mu\textrm{g}$.hr.ml$^{-1}$이었다. 복강내 주사(1g/kg)의 경우 소실상의 반감기는 3.28hr, AUC는 439.3$\mu\textrm{g}$.hr.ml$^{-1}$이었다. 최고 혈중농도 도달시간은 4.4hr이었으며 그때의 농도는 33.19$\mu\textrm{g}$.ml$^{-1}$이었다. 한편 흡수속도 정수는 0.2493$hr^{-1}$이었다. 정맥내 투여에 대한 복강내 투여의 생체 이용율은 1.1252%로 복강내 투여시 흡수율이 좋지 않음을 시사하고 있다. 이는 투여 시료인 micellar solution이 일종의 약물저장 형태로 작용하여 활성물질을 서서히 방출 하기 때문인 것으로 사료된다. 한편 예비적 대사연구결과 TLC에서 뇨나 담즙으로 배설되는 유의한 농도수준의 ara-CDP-DL-PCA.2Na가 없는 것으로 평가되었다. 이는 생체내에서 enzyme등에 의한 대사과정을 거치는 것으로 사료되는바 방사성 동위원소 표지화합물을 이용한 충분한 대사연구가 필요한 것으로 사료된다.

• Journal of Pharmaceutical Investigation
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• v.41 no.2
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• pp.111-115
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• 2011

pH-sensitive cross-linked polymeric micelles were synthesized by using block ionomer complexes of poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMA) with calcium ions as micellar templates. An anticancer drug, doxorubicin (DOX) was conjugated on the cross-linked ionic cores of micelles via acid-labile hydrozone bonds. The resulting DOX-conjugated, pH-sensitive micelles are stable at physiological conditions, whereas the release of DOX was significantly increased at the acidic pH. Such micelles were internalized to lysosomes, and acidic pH in lysosomes triggers the release of DOX upon internalization in MCF-7 breast cancer cells. The released DOX entered the cell nucleus and eventually killed cancer cells. Therefore, these data demonstrate that the pH-sensitive micelles could be a promising nanocarrier for delivery of anticancer drug, DOX.