• Macromolecular Research
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• v.15 no.5
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• pp.437-442
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• 2007

Poly(ethylene glycol) methyl ether (PEG)-poly(${\beta}$-amino ester) (PAE) block copolymers were synthesized using a Michael-type step polymerization, and the construction of pH-sensitive polymeric micelles (PM) investigated. The ${\beta}$-amino ester block of the block copolymers functioned as a pH-sensitive moiety as well as a hydrophobic block in relation to the ionization of PAE, while PEG acted as a hydrophilic block, regardless of ionization. The synthesized polymers were characterized using $^1H-NMR$, with their molecular weights measured using gel permeation chromatography. The $pK_b$ values of the pH-sensitive polymers were measured using a titration method. The pH-sensitivity and critical micelle concentration (CMC) of the block copolymers in PBS solution were estimated using fluorescence spectroscopy. The pH dependent micellization behaviors with various bisacrylate esters varied within a narrow pH range. The critical micelle concentration at pH 7.4 decreased from 0.032 to 0.004 mg/mL on increasing the number of methyl group in the bisacrylate from 4 to 10. Also, the particle size of the block copolymer micelles was determined using dynamic light scattering (DLS). The DLS results revealed the micelles had an average size below 100 nm. These pH-sensitive polymeric micelles may be good carriers for the delivery of an anticancer drug.

• Bulletin of the Korean Chemical Society
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• v.31 no.8
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• pp.2265-2271
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• 2010

In this study, wormorm-like polymeric micelles were construted from poly(L-lactic acid)-b-poly(ethyelen glycol) (PLLA-b-PEG) block copolymers via worm-like (or cylindrical) self- assembly that consisted of a relatively long PLLA block ($M_n$ 7K Daltons) at the core and a relatively short PEG block ($M_n$ 2K Daltons) as the shell. Several cancer-targeting moieties (such as folate, cobalamin, and cyclic arginine-glycine-aspartic (RGD) peptide) were chemically coupled with the succinylated or maleimided PEG block of PLLA-b-PEG to act as a cancer cell-specific targeting ligand for breast cancer. The worm-like micelles with muplite cancer cell-specific ligands proved to be successful in recognizing different breast cancer cells at once. This has the potential to aid in cancer-specific drug delivery and to be used as an effective treatment for breast cancer.

• Macromolecular Research
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• v.11 no.1
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• pp.2-8
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• 2003

The self-assembly of polymers can lead to supramolecular systems and is related to the their functions of material and life sciences. In this article, self-assembly of Langmuir-Blodgett (LB) films, polymer micelles, and polymeric nanoparticles, and their biomedical applications are described. LB surfaces with a well-ordered and layered structure adhered more cells including platelet, hepatocyte, and fibroblast than the cast surfaces with microphase-separated domains. Extensive morphologic changes were observed in LB surface-adhered cells compared to the cast films. Amphiphilic block copolymers, consisting of poly(${\gamma}$-benzyl L-glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) [or poly(N-isopropylacrylamide) (PNIPAAm)] as the hydrophilic one, can self-assemble in water to form nanoparticles presumed to be composed of the hydrophilic shell and hydrophobic core. The release characteristics of hydrophobic drugs from these polymeric nanoparticles were dependent on the drug loading contents and chain length of the hydrophobic part of the copolymers. Achiral hydrophobic merocyanine dyes (MDs) were self-assembled in copolymeric nanoparticles, which provided a chiral microenvironment as red-shifted aggregates, and the circular dichroism (CD) of MD was induced in the self-assembled copolymeric nanoparticles.

• 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).

• Macromolecular Research
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• v.10 no.1
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• pp.49-52
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• 2002

Rod-coil amphiphilic block copolymers, PALG-PEOs, poly(alkyl $\alpha$, L-glutamate-co-ethylene oxide)s, were successfully synthesized in three steps: 1) esterification of L-glutamic acid, 2) synthesis of ${\gamma}$-alkyl L-gultamate N-carboxyanhydride, and 3) polymerization of NCA monomers. These molecules form polymeric micelles with the hydrophobic core and hydrophilic corona in aqueous solution, which were characterized by light scattering and static fluorescence measurement.

• Journal of the Korean Chemical Society
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• v.42 no.1
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• pp.92-98
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• 1998

Poly(DL-lactide-co-glycolide) (80:20) was synthesized from DL-lactide and glycolide, and the copolymers was made to micelles containing clonazepam for drug delivery system. The release experiments of the drug from micelles were operated at pH 7.4 phosphate buffer solution $37.0{\pm}0.05^{\circ}C$. The linearly-releasing time ranges of the drug from micelles prepared with the copolymer/drug weight ratio of 20:40, 20:20, and 40:20 (mg) were 50, 41, and 29 days, respectively. So the linearly-releasing time of drug showed the order of micelles 20/40 > micelles 20/20 > micelles 40/20. In short, the formulation allows polymeric micelles to suppress the burst effect of the drug release mechanism, which led to the controlled release pattern and the possibility of drug delivery system for veinous injection.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.56-57
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• 2006

The ultra pH-sensitive polymeric mixed micelles based on poly(L-histidine) chemistry and constructed from block copolymers containing polyHis, present four functionalities as decreasing pH: ligand exposure at pH 7.0, micelle destabilization below pH 6.8, enhanced DOX release and endosomal membrane disruption. The first functionality is expected to endow tumor pH specificity to nonspecific ligands and the rest ones may help to treat solid tumors that are hard-to-treat by conventional chemotherapy (resistant tumors). The concept was proven in vitro studies and in vivo model.

• Macromolecular Research
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• v.12 no.1
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• pp.63-70
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• 2004

We have synthesized various types of poly(ethylene glycol) (PEG)-ibuprofen conjugates by the nucleophilic substitution of bromo-terminated PEG with ibuprofen-Cs salt; PN (Pluronic) was also used in place of PEG. All the bromo-terminated PEGs and PN were obtained in high yield. Conversions of the terminal hydroxyl groups to bromo-termini were quantitative, as were the drug conjugation processes. The Ι$_1$/Ι$_3$values obtained from solutions of the ibuprofen-conjugated prodrugs are summarized in relation to those of ibuprofen in water and in aqueous solutions of the original PEG, PN, and several ordinary surfactants. We believe that the fully hydrophilic PEG is completely hydrated and forms no hydrophobic pocket by segment aggregation. These results indicate that the probe environment is significantly hydrophobic, particularly in the solution of prodrug PN, for which the ratio is similar to that obtained from typical micelles of surfactants. The results suggest, therefore, that the present synthetic method is very useful for preparing PEG-based prodrugs from pharmaceuticals having carboxyl functionalities.

• Journal of Pharmaceutical Investigation
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• v.39 no.6
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• pp.393-400
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• 2009

PHEA (hydroxyethyl-aspartamide)-mPEG (methoy-polyethyleneglycol)-$C_{16}$ (hexadecylamine)-ED (ethylenediamine) was prepared as a drug delivery carrier. The structure and molecular weight of polymers were characterized by $^1H$-NMR and gel permeation chromatography. Micelle size and shape were measured by electro-photometer light scattering and transmission electron microscope. The mean diameter of micelles was 23 nm in aqueous solution. To evaluate the potential of these polymeric micelles as a drug carrier, PSI-mPEG-$C_{16}$-ED was conjugated with Cy5.5 for Near-Infrared Fluorescent (NIRF) based optical imaging. PSI-mPEG-$C_{16}$-ED-Cy5.5 was injected intravenously into mice (n=5) and in vivo NIRF imaging was performed during 48 h after injection. The biodistribution study at 24 h after injection showed the longcirculation property of PSI-mPEG-$C_{16}$-ED-Cy5.5. Therefore, PSI-mPEG-$C_{16}$-ED micelles could be a promising drug carrier and imaging agent.

• Polymer(Korea)
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• v.34 no.3
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• pp.274-281
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• 2010

In this study, PEG-PLA(or PLGA) amphiphilic di-block copolymers were synthesized by ring opening polymerization of D,L-lactide(or glycolide) and applied to polymeric micelle system for solubilization of a rosiglitazone as diabetes drug. The drug could be efficiently loaded into the polymer micelle by solid dispersion technique, and the drug-loaded micelles were characterized and evaluated as a drug delivery carrier by fluorescence spectrometer, DSC, and DLS measurements. The colloidal stability of drug loaded micelles in aqueous media could be enhanced by addition of 2-hydroxy-N-picolylnitinamide as a hydrotropic agent. The polymer micelles also showed biocompatible and nontoxic properties in vitro cell viability using MTT assay, and the drug loaded micelles were observed to be more effective than free drug for decreasing glucose in blood of rats.