• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.333-336
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• 2005

The objective of this study was to investigate the stability of tetracycline HCl on encapsulation into and inside reverse micelles. To do so, tetracycline HCl was first mixed with cetyltrimethylammonium bromide, water and ethyl formate to make reverse micelles. The degradation kinetics of tetracycline HCl inside the reverse micelles was then assessed by scrutinizing its stability data. Under our experimental conditions, the reverse micelles formed spontaneously in absence of any mixing devices. During the preparation of the reverse micelles, however, considerable portions of tetracycline HCl underwent a chemical reaction (e.g., epimerization). For instance, $51.4{\pm}0.6%$ of an initial concentration of tetracycline HCl was transformed into a degradation product. Once dissolved inside the reverse micelles, the degradation of tetracycline HCl followed an exponential decay pattern. The plot of log{the degradation rate of tetracycline HCl} versus log{tetracycline HCl concentration} made it possible to determine the order of degradation reaction and rate constant. It was proven that the degradation of tetracycline HCl inside the reverse micelles followed a first order kinetics with a rate constant of 0.0027 $hour^{-1}$. Meriting further investigation might be formulation studies to stabilize tetracycline HCl on encapsulation into and inside the reverse micelles.

• Macromolecular Research
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• v.17 no.11
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• pp.926-930
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• 2009

A new method for encapsulating nanomaterials within intermediary layer cross-linked (ILCL) polymeric micelles using a bifunctional photo-cross-linking agent was developed. For ILCL polymeric micelles, an amphiphilic triblock copolymer of poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate)-b-poly(methyl methacrylate) (PEG-PHEMA-PMMA) was synthesized via consecutive atom transfer radical polymerization (ATRP), Di(4-hydroxyl benzophenone) dodecanedioate (BPD) was used as a bifunctional photo-cross-linking agent. The PMMA-tethered Au nanoparticles and BPD, or pyrene and BPD were encapsulated in the PEG-PHEMA-PMMA micelles, and their intermediary layers were photo-cross-linked by UV irradiation for 1 h. The HEMA units donated labile hydrogens to the excited-state benzophenone groups in BPD, and they were subsequently cross-linked by BPD through radical-radical combination. The spherical structures of the PEG-PHEMA-PMMA micelles containing the Au nanoparticles or pyrene were unaffected by the photo-cross-linking process.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.101-101
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• 2006

We have studied the micellisation of poly(n-butyl acrylate)-block-poly(acrylic acid) and poly(n-butyl acrylate)-graft-poly(acrylic acid) in aqueous solution. The size and structure of the formed micelles was elucidated by scattering and imaging techniques. The micelle structure depends on pH, composition, and topology: graft copolymers form much smaller micelles that block copolymers of similar composition. We have also synthesized block copolymers of acrylic acid and N-isopropylacrylamide (NIPAAm) or N,N-diethylacrylamide (DEAAm). Due to the LCST of polyNIPAAm and polyDEAAm, these block copolymers spontaneously form micelles upon heating and they form inverse micelles upon decreasing pH below 4. If the LCST block is much longer than the PAA one, this presents a very convenient way to prepare crew-cut micelles. The polymers have been successfully used as stabilizers in emulsion polymerization. They also have been conjugated to streptavidin. The conjugates reversibly form mesoscopic particles on heating.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.10 no.1
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• pp.13-23
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• 1984

The fluorescence intensity rations (F2.F1) of excimer (F2) to monomer (F1) of pyrene were measured as a function of the concentration of sodium dodecyl sulfate (SDS). It was found that there were not gross changes in size and shape of sphere-shape micelles in the first micelle concentration, while at concentrations above the second critical micelle concentration (CMC) the micelles grew in size with increasing concentration. Fluorescence intensities of 8-anilinonaphthalene 1-sulfonate (ANS) were also monitored as a micellar probe with varying concentrations of SDS. Results suggested that a phase transition from sphere-shaped micelles to hemicapped rod-like micelles occurred at the second CMC (17). A general formula for the axial ratio of ellip-soil-shaped micelle in the first micelle concentration was suggested. According to this general formula, the axial ratio of SDS, sodium lauryl ether sulfate and sodium laurate were 1:1, 5:2, and 5:3, respectively. The electrolyte-induced phase transition from spherical to hemicapped rod-like micelles occurred and the size of hemicapped rod-like micelles grew with increasing electrolyte concentrations. The maximum concentrations of solubilzed benzene in sphere-shaped micelles and hemicapped rod-like micelles were measured by differential spectrohpotometry. The hemicapped rod-like micelles in the presence of electrolytes grew in size with increasing amount of benzene solubilized.

• Bulletin of the Korean Chemical Society
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• v.34 no.2
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• pp.558-564
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• 2013

A simple and effective method is introduced to synthesize a series of polystyrene-b-poly(oligo(ethylene oxide) monomethyl ether methacrylate)-b-polystyrene (PSt-b-POEOMA-b-PSt) triblock copolymers. The structures of PSt-b-POEOMA-b-PSt copolymers were characterized by Fourier-transform infrared spectroscopy (FTIR) and nuclear magnetic resonance ($^1H$ NMR) spectroscopy. The molecular weight and molecular weight distribution of the copolymer were measured by gel permeation chromatography (GPC). Furthermore, the self-assembling and drug-loaded behaviours of three different ratios of PSt-b-POEOMA-b-PSt were studied. These copolymers could readily self-assemble into micelles in aqueous solution. The vitamin E-loaded copolymer micelles were produced by the dialysis method. The micelle size and core-shell structure of the block copolymer micelles and the drug-loaded micelles were confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The thermal properties of the copolymer micelles before and after drug-loaded were investigated by different scanning calorimetry (DSC). The results show that the micelle size is slightly increased with increasing the content of hydrophobic segments and the micelles are still core-shell spherical structures after drug-loaded. Moreover, the glass transition temperature (Tg) of polystyrene is reduced after the drug loaded. The drug loading content (DLC) of the copolymer micelles is 70%-80% by ultraviolet (UV) photolithography analysis. These properties indicate the micelles self-assembled from PSt-b-POEOMA-b-PSt copolymers would have potential as carriers for the encapsulation of hydrophobic drugs.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.9-13
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• 2013

The aim of the present study was to examine the effect of micellar systems on the absorption of beta-lapachone (b-lap) through different intestinal segments using a single-pass rat intestinal perfusion technique. B-lap was solubilized in mixed micelles composed of phosphatidylcholine and sodium deoxycholate, and in sodium lauryl sulfate (SLS)-based conventional micelles. Both mixed micelles and SLS micelles improved the in situ permeability of b-lap in all intestinal segments tested although the mixed micellar formulation was more effective in increasing the intestinal absorption of b-lap. The permeability of b-lap was greatest in the large intestinal segments. Compared with SLS micelles, the effective permeability coefficient values measured with mixed micelles were 5- to 23-fold higher depending on the intestinal segment. Our data suggest that b-lap should be delivered to the large intestine using a mixed micellar system for improved absorption.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7363-7369
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• 2014

The present study aimed to prepare and evaluate polymeric micelles conjugated with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups for antitumor efficacy. The isomeric block copolymers, ${\alpha}$- and ${\gamma}$-folate-polyethyleneglycol-distearoyl phosphatidylethanolamine (${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE), were produced by solid phase peptide synthesis. Three types of doxorubicin (DOX)-loaded polymeric micelles (MPEG-DSPE-DOX and ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPEDOX micelles) were prepared via the film formation method. Compared with MPEG-DSPE-DOX micelles, the ${\alpha}$- / ${\gamma}$-Fol-PEG-DSPE-DOX micelles presented a higher cellular uptake behavior in the live cell study. Cell viability percentages were 81.8%, 57.3%, 56.6% at 2 hours for MPEG-DSPE-DOX, ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles, respectively (p<0.05). Using the KB xenograft tumor model, both ${\alpha}$- and ${\gamma}$-folate-conjugated micelles were found to have better antitumor effects with lower toxicity in comparison with MPEG-DSPE-DOX micelles. No difference in in vivo antitumor efficacy was found between ${\alpha}$- and ${\gamma}$-Fol-PEG-DSPE-DOX micelles. The folate-conjugated micelles might be a potentially useful strategy for tumor targeting of therapeutic agents, whether grafting with folic acid through ${\alpha}$- or ${\gamma}$-carboxyl groups.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.54-55
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• 2006

Polymeric micelles, supramolecular assemblies of block copolymers, are useful nanocarriers for the systemic delivery of drugs and genes. Recently, novel polymeric micelles with various functions such as the targetability and stimuli-sensitivity have been emerged as promising carriers that enhance the efficacy of drugs and genes with minimal side effects. This presentation focuses our recent approach to the preparation of functional block copolymers that are useful for constructing smart micellar delivery systems in advanced therapeutics, including chemo-gene therapy. Particular emphasis is placed on the characteristic behaviors of intracellular environment-sensitive micelles that selectively exert drug activity and gene expression in live cells.

• Macromolecular Research
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• v.17 no.2
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• pp.99-103
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• 2009

We evaluated the efficacy of pH-sensitive micelles, formed by methoxy poly(ethylene glycol)-b-poly($\beta$)-amino ester) (PEG-PAE), as carriers for paclitaxel (PIX), a drug currently used to treat various cancers. PTX was successful encapsulated by a film hydration method. Micelles encapsulated more than 70% of the PTX and the size of the PTX-encapsulated micelles (PTX-PM) was less than 150 nm. In vitro experiments indicated that the micelles were unstable below pH 6.5. After encapsulation of PTX within the micelles, dynamic light scattering (DLS) studies indicated that low pH had a similar demicellization effect. An in vitro release study indicated that PTX was slowly released at pH 7.4 (normal body conditions) but rapidly released under weakly acidic conditions (pH 6.0). We demonstrated the safety of micelles from in vitro cytotoxicity tests on HeLa cells and the in vivo anti-tumor activity of PTX-PM in B16F 10 tumor-bearing mice. We concluded that these pH-sensitive micelles have potential as carriers for anti-cancer drugs.