• 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.

• Polymer(Korea)
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• v.33 no.2
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• pp.137-143
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• 2009

We prepared norfloxacin (NFX)-incorporated polymeric micelle using poly ($\varepsilon$-caprolactone)/poly(ethylene glycol) (PCL/PEG, CE) diblock copolymers. Particle size was from 60 to 200 nm according to the PCL block length. Their critical association concentration (CAC) was decreased according to the increase of PCL block length. $^1H$-NMR study showed core-shell type micelle structures of CE diblock copolymers in the aqueous environment. Drug release from polymeric micelle was continued over 2 days. Duration of drug release was varied according to the PCL block length and drug contents. At antimicrobial activity test, polymeric micelle showed almost similar cytotoxicity compared to NFX itself.

• Bulletin of the Korean Chemical Society
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• v.21 no.4
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• pp.383-388
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• 2000

Multiblock copolymers consisting of poly( g-benzyl L-glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) as the hydrophilic part (GEG) were synthesized and characterized. GEG polymeric micelles were prepared by the dialysis technique. Particle size distributions based on intensity,volume, and number-average were 22.6 $\pm$ 11.9 nm, 23.5 $\pm$ 4.6 nm, and 23.7 $\pm$ 37 nm, respectively. It was observed that par-ticle size and size distribution of GEG polymeric micelles changed significantly with the choice of initial sol-vent. Transmission electron micrographs (TEM) showed the polymeric micelles to be spherically shaped, with sizes ranging from 20 nm to 40 nm in diameter. Fluorescence spectroscopy measurements suggested that GEG block copolymers wereassociated in water to form polymeric micelles, and the critical micelle concentrations (CMC) value of the block copolymers was 0.0094 g/L. Further evidenceof micelle formation of GEG block copolymers and limited mobility of the PBLG chain in the core ohe micelle was obtained with 1 H NMR in D2O.

• Macromolecular Research
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• v.17 no.7
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• pp.538-543
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• 2009

In this study, methotrexate (MTX)-encapsulated polymeric micelles using methoxy poly(ethylene glycol) (MPEG)-grafted chitosan (ChitoPEG) copolymer were prepared. The MIX-incorporated polymeric micelles of ChitoPEG copolymer has a particle size of around 50-100 nm. In 1H nuclear magnetic resonance (NMR) study, the specific peaks of MTX disappeared in heavy water ($D_2O$) and only the specific peak of MPEG was observed, while all of the peaks were confirmed in dimethyl sulfoxide (DMSO). These results indicated that MTX was complexed with chitosan and then formed an ion complex inner-core of the polymeric micelle in an aqueous environment. The drug contents of the polymeric micelle were around $4{\sim}12%$ and the loading efficiency of MTX in the polymeric micelles was higher than 60% (w/w) for all of the formulations. The cytotoxicity of MIX and MTX-incorporated polymeric micelle against CT26 tumor cells was not significantly changed.

• Macromolecular Research
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• v.16 no.5
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• pp.418-423
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• 2008

Poly[(R)-3-hydroxy butyrate] (PHB) and methoxy poly(ethylene glycol) (mPEG) were conjugated by the transesterification reaction with tin(II)-ethylhexanoate (Sn(Oct)-II) as a catalyst. Hydrophobic PHB and hydrophilic mPEG formed an amphiphilic block copolymer which was formed with the self-assembled polymeric micelle in aqueous solution. In this study, we tried to determine the optimum ratio of hydrophobic/hydrophilic segments for controlled drug delivery. The particle size and shape of the polymeric micelle were measured by atomic force microscopy (AFM) and transmission electron microscopy (TEM). Their size were 61-102 nm with various block ratios. Griseofulvin was loaded in the polymeric micelle as a hydrophobic model drug. The loading efficiency and release profile were measured by high performance liquid chromatography (HPLC). The model drug in our system was constantly released for 48 h.

• 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.19 no.9
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• pp.962-967
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• 1998

Block copolymers consisting of poly(rbenzyl L-glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) as the hydrophilic part were synthesized and characterized. Polymeric micelles of the block copolymers (abbreviated GEG) were prepared by a dialysis method. The GEG block copolymers were associated in water to form polymeric micelles, and the critical micelle concentration (CMC) values of the block copolymers decreased with increasing PBLG chain length in the block copolymers. Transmission electron microscopy (TEM) observations revealed polymeric micelles of spherical shapes. From dynamic light scattering (DLS) study, sizes of polymeric micelles of GEG-1, GEG-2, and GEG-3 copolymer were 106.5±59.2 nm, 79.4±46.0 nm, and 37.9±13.3 nm, respectively. The drug loading contents of GEG-1, GEG-2 and GEG-3 polymeric micelles were 12.6, 11.9, and 11.0 wt %, respectively. These results indicated that the drugloading contents were dependent on PBLG chain length in the copolymer; the longer the PBLG chain length, the more the drug-loading contents. Release of norfloxacin (NFX) from the nanoparticles was slower in higher loading contents of NFX than in lower loading contents due to the hydrophobic interaction between PBLG core and NFX.

• Bulletin of the Korean Chemical Society
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• v.30 no.4
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• pp.931-934
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• 2009

• Polymer(Korea)
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• v.24 no.6
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• pp.854-859
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• 2000

The synthesis of poly(N,N-dimethylamino ethyl methacrylate (DMAEMA)-block-poly(ethylene glycol) (PEG)) copolymer has been carried out and the block copolymer was characterized by FT-IR, DSC, and $^1$H-NMR. The formation of polymeric nanoaggregation was observed in the solution mixture of poly(DMAEMA) -block-PEG copolymer and poly (ethyl acrylamide) (EAAm) due to the intermolecular interaction via hydrogen bond between DMAEMA and poly(EAAm). The formation of polymeric nanoaggregation was observed above critical micelle concentration (CMC).

• 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.