• Macromolecular Research
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• v.13 no.4
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• pp.344-351
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• 2005

pH-sensitive block copolymers were synthesized by coupling reaction of sulfamethazine and amphiphilic diblock copolymer, and their micellization-demicellization behavior was investigated. Sulfamethazine (SM), a derivative of sulfonamide, was introduced as a pH responsive moiety while methoxy poly(ethylene glycol)poly(D,L-lactide) (MPEG-PDLLA) and methoxy poly(ethylene glycol)-poly($D,L-lactide-co-{\varepsilon}-caprolactone$) (MPEG-PCLA) were used as biodegradable amphiphilic diblock copolymers. After the sulfamethazine was carboxylated by the reaction with succinic anhydride, the diblock copolymer was conjugated with sulfamethazine by coupling reaction in the presence of DCC. The critical micelle concentration (CMC) and mean diameter of the micelles were examined at various pH conditions through fluorescence spectroscopy, dynamic light scattering and transmission electron microscopy. For MPEG-PDLLA-SM and MPEG-PCLA-SM solutions, the pH-dependent micellization-demicellization was achieved within a narrow pH band, which was not observed in the MPEG-PDLLA and MPEG-PCLA solutions. The micelle showed a spherical morphology and had a very narrow size distribution. This pH-sensitive block copolymer shows potential as a site-targeted drug carrier.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.263-263
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• 2006

Poly (ethylene glycol)(PEG) - Poly (${\varepsilon}-caprolactone(CL)$) - Poly (D,L lactide(LA) (PCLA-PEG-PCLA) was synthesized by ring-opening polymerization to form temperature sensitive hydrogel triblock copolymer. The triblock copolymer was acrylated by acryloyl chloride. ${\beta}-amino$ ester was used as a pH sensitive moiety, in this study ${\beta}$- amino ester obtained from 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine, it have pKb around 6.6. pH/temperature sensitive penta-block copolymer (PAE-PCL-PEG-PCL-PAE) was synthesized by addition polymerization from acrylated triblock copolymer, 1,4-butandiol diacrylate, and 4, 4' trimethylene dipiperidine. Their physicochemical properties of triblock and penta-block copolymers were characterized by $^1H-NMR$ spectroscopy and gel permeation spectroscopy. Sol-gel phase transition behavior of PAE-PCL-PEG-PCL-PAE block copolymers were investigated by remains stable method. Aqueous media of the penta-block copolymer (at 20 wt%) changed from a sol phase at pH 6.4 and $10^{\circ}C$ to a gel phase at pH 7.4 and $37^{\circ}C$. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereo-regularity of the hydrophobic of the block copolymer, and the ionization of the pH function groups in the copolymer depended on the changing of environmental pH, respectively. The degradation and the stabilization at pH 7.4 and $37^{\circ}C$, and the stabilization at pH 6.4 and $10^{\circ}C,\;5^{\circ}C,\;0^{\circ}C$, of the gel were determined. The results of toxicity experiment show that the penta block copolymer can be used for injection drug delivery system. The sol?gel transition of this block copolymer also study by in vitro test ($200{\mu}l$ aqueous solution at 20wt% polymer was injected to mouse). Insulin loading and releasing by in vitro test was investigated, the results showed that insulin can loading easily into polymer matrix and release time is around 14-16days. The PAE-PCL-PEG-PCL-PAE can be used as biomaterial for drug, protein, gene loading and delivery.

• Macromolecular Research
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• v.11 no.1
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• pp.42-46
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• 2003

Cell attachment and proliferation on the polymer films of triblock copolymer(ester-ether)s comprising po1y (L-1actide) (PLLA) and poly (oxyethylene-co-oxypropylene)(PN) were investigated using 3T3 fibroblasts. It was found that on the tissue culture polystyrene(TCPS) and the PLLA control film the cells could spread well while on the copolymer films the cells showed a rounded morphology without spreading and proliferated weakly. Especially, little cells proliferated on the films of copolymer having a LN composition of 20 wt%. While the water absorption of the copolymer films increased with increasing PN content, the contact angle against water of copolymer films immersed in aqueous medium was almost identical, being slightly lower than that of the PLLA film. These properties were compatible with the results of cell attachment. The in vitro hydrolysis of the films of triblock and multiblock type copolymers was faster with increasing PN content. The increased hydrolyzability, the flexibility and the decreased cell attachment suggested that these copolymers may have high potential as biodegradable materials for medical use.

• Macromolecular Research
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• v.10 no.2
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• pp.85-90
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• 2002

Poly (ethylene oxide)/polylatide/poly(ethylene oxide) (PEO/PL/PEO) tri-block copolymers, which each block is connected by ester bond, were synthesized by coupling reaction of PL with PEO in the presence of pyridine. PL/PEO/PL tri-block copolymer was synthesized by ring opening polymerization of L-lactide initiated by PEO in the presence of stannous octoate. Degradation behavior of the copolymers was investigated in a pH 7.4 phosphate buffer saline (PBS) at 37$\pm$1 $^{\circ}C$. Gel permeation chromatography (GPC) and $^1$H-nuclear magnetic resonance (NMR) were used to monitor the change of mass loss, molecular weight and composition of copolymers. In hydrolytic degradation, the PEO/PL/PEO tri-block copolymer with high PEO contents affected the increase of its mass loss, and resulted in the decrease of its molecular weight as well as PEO composition. However, when PL/PEO/PL and PEO/PL/PEO tri-block copolymers had similar PEO contents, PEO/PL/PEO decreased faster in molecular weight and PEO composition than PL/PEO/PL.

• 한국생물공학회:학술대회논문집
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• 2005.10a
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• pp.711-712
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• 2005

• Macromolecular Research
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• v.14 no.3
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• pp.359-364
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• 2006

Di-block copolymers composed of two biocompatible polymers, poly(ethylene glycol) and poly(D,L-lactide), were synthesized by ring-opening polymerization for preparing polymer vesicles (polymersomes). Emulsion solvent evaporation method was used to fabricate the polymersomes. Scanning electron microscope (SEM) images confirmed that polymersomes have a hollow structure inside. Confocal laser microscope and optical microscope were also used to verify the hollow structure of polymersomes. Polymersomes having various sizes from several hundred nanometers to a few micrometers were fabricated. The size of the polymersomes could be readily controlled by altering the relative hydrodynamic volume fraction ratio between hydrophilic and hydrophobic blocks in the copolymer structure, and by varying the fabrication methods. They showed greatly enhanced stability with increased molecular weight of PEG. They maintained their physical and chemical structural integrities after repeated cycles of centrifugation/re-dispersion, and even after treatment with surfactants.

• Polymer(Korea)
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• v.30 no.6
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• pp.512-518
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• 2006

A biodegradable polymer poly((R) -3-hydroxybutyric acid) (PHB) was conjugated with a hydrophilic polymer poly(ethylene glycol) (PEG) by the ttansesterification reaction to form the amphiphilic block copolymer. PHB with low molecular weight ($3000{\sim}30000$) was appropriated for the drug delivery materials. High molecular weight PHB was hydrolyzed by an acid-catalyst to produce the low molecular weight one. Amphiphilic block copolymer was formed the self-assembled polymeric micelle system in the aqueous solution that the hydrophillic PEG was wraped the hydrophobic PHB. Generally, polymeric micelle forms the small particle between $10{\sim}200nm$. These polymeric micelle systems have been widely used for the drug delivery systems because they were biodegradable, biocompatible, non-toxic and patient compliant. The hydroxyl group of PEG was substituted with carboxyl group which has the reactivity to the ester group of PHB. Amphiphilic block copolymer was conjugated between PHB, and modified PEG at $176^{\circ}C$ which was higher than the melting point of PHB. Transesterification reaction was verified with DSC, FTIR, $^1H-NMR$. In the aqueous solution, critical micelle concentration (CMC) of the mPEG-co-PHB copolymer measured by the fluororescence scanning spectrometer was $5{\times}10^{-5}g/L$. The shape and size of the nanoparticle was taken by dynamic light scattering and atomic force microscopy. The size of the nanoparticle was about 130 nm and the shape was spherical. Our polymeric micelle system can be used as the passive targeting drug delivery system.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1638-1642
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• 2012

A series of poly (lactic acid) (PLA) and poly (ethylene glycol) (PEG) tri and multiblock copolymers with relatively high molecular weights were synthesized through the coupling reaction between the bis(acyl chloride) of carboxylated PLA and mono or dihydroxy PEG. The coupling reaction and the copolymer structures were monitored by nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC). The melting temperature (Tm) of PEG blocks decreased with the presence of PLA sequences attaching to PEG blocks. The CMC values were determined to be 10-145 mg/L depending on the length of PLA and PEG blocks and the structure of the block copolymers.

• Macromolecular Research
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• v.15 no.7
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• pp.646-655
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• 2007

To achieve targeted drug delivery for chemotherapy, a ligand-mediated nanoparticulate drug carrier was designed, which could identity a specific receptor on the surfaces of tumor cells. Biodegradable poly(ethylene oxide)/poly$({\varepsilon}-caprolactone)$ (PEG/PCL) amphiphilic block copolymers coupled to biotin ligands were synthesized with a variety of PEG/PCL compositions. Block copolymeric nanoparticles harboring the anticancer drug paclitaxel were prepared via micelle formation in aqueous solution. The size of the biotin-conjugated PEG/PCL nanoparticles was determined by light scattering measurements to be 88-118 nm, depending on the molecular weight of the block copolymer, and remained less than 120 nm even after paclitaxel loading. From an in vitro release study, biotin-conjugated PEG/PCL nanoparticles containing paclitaxel evidenced sustained release profiles of the drug with no initial burst effect. The biotin-conjugated PEG/PCL block copolymer itself evidenced no significant adverse effects on cell viability at $0.005-1.0{\mu}g/mL$ of nanoparticle suspension regardless of cell type (normal human fibroblasts and HeLa cells). However, biotin-conjugated PEG/PCL harboring paclitaxel evidenced a much higher cytotoxicity for cancer cells than was observed in the PEG/PCL nanoparticles without the biotin group. These results showed that the biotin-conjugated nanoparticles could improve the selective delivery of paclitaxel into cancer cells via interactions with over-expressed biotin receptors on the surfaces of cancer cells.

• Polymer(Korea)
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• v.33 no.6
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• pp.515-519
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• 2009

Biodegradable poly((R)-3-hydroxy butyrate) and poly(ethylene glycol) was conjugated to make amphiphilic di-block copolymer. Folate was conjugated at di-block copolymer to target the cancer cells. Copolymer was ready to form the self-assembled micelle whose size was 125~156 nm in aqueous solution. Griseofulvin as a hydrophobic drug was loaded in nanoparticles. Their loading efficiencies were 35~56%. Hydrophobic drug was continuously released for 24 h. Cell viability test showed that folate attached particles were 10% more efficient than the particles without targeting ligands.