• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.7-12
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• 2001

Amphotericin B (AmB) is a drug of choice for the treatment of systemic fungal diseases, but its use is considerably limited due to a high incidence of toxicity, particularly nephrotoxicity. It has been demonstrated that the toxicity of AmB is caused by self-aggregated species of the drug and that unaggregated (monomeric) drug is nontoxic but still expresses antifungal activity. Poly (ethylene oxide) (PEO) is a water-soluble polymer, which may impact the aggregation state of AmB. We have studied the aggregation state of AmB as a function of PEO molecular weight and concentration. At 3,000 and 8,000 g/mole, there was minimal or no change of critical aggregation concentration (CAC) of AmB regardless of the concentration of polymer. By contrast at 20,000 g/mole, the CAC of AmB strikingly increased to 24.3 and $37.5\;{\mu}M$ at 5.0% and 10 % w/v of polymer, respectively. The critical overlap concentration (COC) of PEO 20,000 g/mole was 5.5%. It appears that an interaction between monomeric AmB and polymer coil increases above the COC, competing with self-aggregation of the drug. Accordingly, the degree of aggregation of AmB stayed low and the toxicity became less. There was no such effect at 3,000 and 8,000 g/mole of PEO, owing perhaps to small dimensions in comparison to AmB. Based upon these findings, less toxic AmB formulation may be developed by a pharmaceutical technique such as solid dispersion system containing both AmB and PEO 20,000 g/mole.

• Journal of Pharmaceutical Investigation
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• v.31 no.1
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• pp.1-5
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• 2001

The aggregation behavior of nystatin (NYS) in the presence of pluronic F127, triblock copolymer of poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO), was measured and correlated with hemolytic activity. Antifungal activity was also studied using Saccharomyces cerevisiae as a model strain. The critical aggregation concentrations (CAC) of the drug were 50.1, 108.0, 134.2, 154.3, and $217.9\;{\mu}M$ at 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% pluronic F127 solution, respectively. The levels of NYS required to start lysis of erythrocytes were about 80, 100, 125, 150, and $200\;{\mu}M$ at 0.1%, 0.5%, 1.0%, 1.5%, and 2.0% pluronic F127 solution, respectively. It was $50\;{\mu}M$ in the absence of the polymer. Minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) of NYS-pluronic F127 lyophilizate were same at $3\;{\mu}g/ml$, while MIC and MFC of pure NYS are $3\;{\mu}g/ml$ and $12\;{\mu}g/ml$, respectively. By modulating the aggregation behavior of NYS, pluronic F127 was able to reduce the toxicity of the drug without compromising the MIC and MFC.

• Journal of Microbiology and Biotechnology
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• v.6 no.6
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• pp.456-460
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• 1996

Recombinant Pseudomonas lipase was used to study protein aggregation and adsorption upon in vitro refolding. Protein adsorption as well as aggregation was responsible for major side reactions upon in vitro refolding as a function of protein concentration. The optimal range of protein concentration was determined by the relative contribution of protein aggregation and adsorption. Above the optimal range, the yield of active lipase inversely correlated with protein aggregation, showing a competition between folding and aggregation. However, adsorption of protein rather than protein aggregation is thought to contribute as a major side reaction of the refolding process at sub-optimal concentrations at which the formation of aggregates should be more reduced. Protein aggregation was influenced by the amount of guanidine hydrochloride in the refolding solvent. The refolding temperature was a critical factor determining the extent of protein aggregation. The refolding yield was also affected by the dilution fold and dilution mode, which suggests that the refolding process might kinetically compete with the rate of mixing.

• Polymer(Korea)
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• v.28 no.2
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• pp.154-161
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• 2004

Modified poly(4-vinylpyridine) was obtained by partial quarternization of nitrogen atoms in pyridine rings of poly(4-vinylpyridine) with methyl group. By means of laser light scattering and fluorescence, it was found that this modified polymer chains were aggregated in the aqueous solution and its structure was core-shell type. The hydrophobic parts of the chains were densely condensed in core part and the hydrophilic part of quarternized amino with positive charge formed the shell part. In the mixed system of modified poly(4-vinylpyridine) and anionic surfactant, sodium dodecyl sulfate, it was observed that a critical aggregation concentration existed and that this critical concentration was suddenly decreased above 0.1 M NaCl. The size change of aggregates was also investigated by dynamic light scattering while sodium dodecyl sulfate was added into polymer solution upto the critical aggregation concentration.

• Journal of the Korean Applied Science and Technology
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• v.30 no.3
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• pp.380-386
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• 2013

N,N,N-Trimethyl-10-nitrophenoxy decylammonium bromide (N10TAB) and N,N,N,N-Tetramethyl-bis-[10-nitrophenoxy decyl]-1,6-hexanediammonium dibromide (N10-6-10N), bearing aromatic nitrophenoxy group in the end of their hydrophobic chains have been prepared, and their properties in aqueous solutions have been studied by conductivity and H-NMR spectroscopy. Below the critical micelle concentration N10-6-10N form premicelle with two or three surfactant molecules. Beyond the critical micelle concentration two molecules have strong self-aggregation ability and form micelles of rather small size and with small aggregation numbers. H-NMR at different concentrations give the informations on the environmental changes of the surfactants on their micellization progress.

• Journal of the Korean Applied Science and Technology
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• v.27 no.4
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• pp.545-551
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• 2010

Hydrophobically monoendcapped poly(sodium acrylate)s formed hydrophobic microdomains in water. This was concluded on poly(sodium acrylate)s with a linear $C_{12}$-alkyl chain attached specifically at the end of the polymer. There was no well defined CMC (critical micelle concentration), but rather a gradual transition from a micelle free solution to a micelle solution. Steady state fluorescence spectroscopy indicates that the micro domains are rather hydrophobic. At pH 5 in the abscence of salt and at pH 9 in the prescence of 1 M sodium citrate the CAC (critical aggregation concentration) was in the range of 0.1 to 2.4 mM. However at pH 5 there was a linear increase in the transition concentration with a head-group size due to an increase in steric and electrostatic repulsions between polymer main chains. At pH 9 in the abscence of salt the transition concentration was in the range of 1 to 80 mM. For the larger polymers there was a effect which consisted of a concentration gradient of sodium counterion toward the hydrophobic domain. The effect was larger for the larger polymers because of the higher total sodium concentration and the less steep counterion concentration gradient.

• Bulletin of the Korean Chemical Society
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• v.28 no.8
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• pp.1425-1428
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• 2007

• Bulletin of the Korean Chemical Society
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• v.21 no.6
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• pp.623-627
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• 2000

Aggregation of hydrophobically end-capped poly(ethylene oxide)s: HEURs, denoted as $C_8$$EO_{380}$$C_8$, $C_12$$CO_{600}$$C_{12}$, and $C_{18}$$EO_{860}$$C_{18}$,are described using static fluorescence, dynamic light scattering, and atomic force microscope (AFM) techniques. The CAC (critical aggregation concentration) was determined by com-paring two fluorescent peaks which were influenced by the polarity of the probe dye molecules, pyrene. The aggregation occurs in concentrations higher than 10 g/L of $C_8$$EO_{380}$$C_8$ and the CAC decreases by increasing the side chain length. The dynamic light scattering experiment shows fast mode and slow mode decays, and both are diffusive. The fast mode does not depend on the concentration, but the slow mode shows concentration dependence influenced by the formation of an aggregated structure. The hydrophobic end groups effect more dominantly than the main chains for the formation of HEUR micelles. By increasing the concentration, the HEUR micelles change their structure from spheres to rodlike micelles, and finally make fused structures, which were visualized with atomic force microscopy.

• Polymer(Korea)
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• v.37 no.3
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• pp.294-301
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• 2013

Polymersomes made of biodegradable triblock copolymers based on poly(fumaric acid-co-sebacoyl chloride)/PEG (PEG-co-P(FA/SC)-co-PEG) were prepared and studied in aqueous solutions. TEM confirmed the formation of vesicles in aqueous media. Aggregation behavior of the copolymers was studied by fluorescence spectroscopy of 8-anilino-1-naphthalenesulfonic acid, and the critical aggregation concentration (c.a.c.) of the copolymer was found to be ${\sim}26.2{\mu}M$ indicating desirable stability of the vesicles. Dynamic light scattering revealed that the size of the vesicles was distributed within the range of 170-270 nm. Turbidity measurements confirmed the relative short-term stability of the polymersomes. Carboxyfluorescein, a hydrophilic compound, was simply encapsulated in the vesicles during polymersome preparation. The release of encapsulant from the polymersomes at 25 and $37^{\circ}C$ lasted about 3 weeks, and the rate of release followed a first-order kinetics. The release is speculated to be primarily carried out through diffusion. These results confirm that these polymersomes are promising as controlled-release carriers of various drugs.

• BMB Reports
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• v.41 no.9
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• pp.635-639
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• 2008

Acrolein is a highly reactive by product of lipid peroxidation and individuals with neurodegenerative disorders have been shown to contain elevated concentrations of this molecule in the brain. In the present study, we examined the pattern of neurofilament-L (NF-L) modification elicited by acrolein. When NF-L was incubated with acrolein, protein aggregation occurred in a acrolein concentration-dependent manner. Exposure of NF-L to acrolein also led to the generation of protein carbonyl compounds. Through the addition of free radical scavengers we observed a significant decrease in acrolein-mediated NF-L aggregation. These results indicate that free radicals may be involved in the modification of NF-L by acrolein. In addition, dityrosine crosslink formation was observed in acrolein-mediated NF-L aggregates and these aggregates displayed thioflavin T reactivity, reminiscent of amyloid. This study suggests that acrolein-mediated NF-L aggregation might be closely related to oxidative reactions, thus these reactions may play a critical role in neuro-degenerative diseases.