• Macromolecular Research
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• 제13권2호
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• pp.147-151
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• 2005

The main objective of this study was to modulate pH-sensitive polymers (poly($\beta-amino esters$)) by controlling their molecular weight during their synthesis. These pH-sensitive and biodegradable polymers were synthesized by Michael-type step polymerization. 1,4-Butane diol diacrylate was used as the unsaturated carbonyl compound and piperazine as the nucleophilic compound. Various molecular weight polymers were obtained by varying the mol ratio of piperazine/1,4-butane diol diacrylate. The synthesized polymers were characterized by $^{1}H-NMR$ and their molecular weights were measured by gel permeation chromatography(GPC). The dependence of the molecular weight on the mol ratio was evaluated by the titration method. Also, the pH dependent turbidity of the polymers was determined by UV-Vis spectrophotometry. This pH dependent property of the polymers could be very useful for preparing drug carriers that are sensitive to pH.

• Journal of Pharmaceutical Investigation
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• 제40권spc호
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• pp.45-61
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• 2010

Polymeric based nanomedicines have been developed for diagnosing, treating, and preventing diseases in human body. The nanosized drug delivery systems having various structures such as micelles, nanogels, drug-conjugates, and polyplex were investigated for a great goal in pharmaceutics: increasing therapeutic efficacy for diseases and decreasing drug toxicity for normal tissues. The functional polymers used for constituting these drug delivery systems should have several favorable properties such as stimuli-responsibility and biodegrdability for controlled drug release, and solublization capacity for programmed drug encapsulation. This review discusses recent developments and trends of functional polymers (e.g., pH-sensitive polymers, biodegradable polymers, and cationic polymers) used for nanosized drug carriers.

• Macromolecular Research
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• 제11권3호
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• pp.189-193
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• 2003

pH- and temperature-sensitive bifunctional hydrogels composed of N-isopropylacrylamide (NiPAAm) and a sulfadimethoxine monomer (SDM) derived from sulfadimethoxine were prepared. These hydrogels exhibit simultaneous pH- and temperature-induced volume-phase transitions. The pH-induced volume-phase transition behavior is produced by the ionization/deionization of SDM and is very sharp. In the high pH region, the ionization of SDM induces swelling of the hydrogels. In the low pH region, the deionization of SDM induces deswelling of the hydrogels. The temperature-induced volume-phase transition behavior of the bifunctional hydrogels exhibits negative thermosensitivity because of the NiPAAm component. The hydrogels swell even at low pH as the temperature decreases. The hydrogels swell at low temperature and high pH, and deswell at high temperature and low pH. The volume of the hydrogels dependl on the balance of the swelling and deswelling produced by the two competing stimuli, pH and temperature.

• Macromolecular Research
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• 제15권5호
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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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• 제23권4호
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• pp.549-554
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• 2002

Thermosensitive poly(organophosphazenes) bearing methoxy-poly(ethylene glycol) (MPEG) and alkylamines as substituents have been synthesized and characterized by elemental analysis, NMR spectroscopy, GPC, and DSC. All the polymers exhibited crystallinity, which was probably induced by the MPEG side chain of the polymers. All the polymers exhibited the lower critical solution temperature (LCSTs) in the range of 28 to $94^{\circ}C$ depending on several factors such as mole ratio of the substituents, kinds of PEG and alkylamines. The higher content of MPEG and shorter chain length of alkylamines of the polymers afforded the higher LCST. The LCSTs of the polymers exhibited almost concentration-independent behavior in the range of 3-30 wt % of the polymers in aqueous solutions. The polymers showed the higher LCSTs in the acidic solutions than in the neutral and basic solutions. The ionic strength of the polymer solution affected the LCST, which decreased with increased NaCl concentration. The polymer bearing almost equimolar substitutuents with the -N-P-N- unit has shown the LCST more sensitive to NaCl and pH than that with the -N-P-O- unit. The polymers were found to degrade in acidic solution but be very stable in alkali solution as well as in the buffer solution of pH 7.4.

• Archives of Pharmacal Research
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• 제28권3호
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• pp.364-369
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• 2005

HPMC (Hydroxypropyl methylcellulose) was chemically modified, using maleic anhydrides, to obtain pH-sensitive HPMCAM (Hydroxypropyl methylcellulose acetate maleate) polymers for use as novel duodenum-specific coating agents. The pharmaceutical properties of HPMCAM, such as film forming, acid values, pH-sensitive values, water vapor permeability, tensile strength and Tg, were investigated, and found to show good film forming properties. The pH­sensitive values were 3.0 to 3.7. In vitro results demonstrate that HPMCAM could completely suppress drug release within 2h in a simulated gastric fluid (pH 1.2) and rapidly release the drug in a simulated pathological duodenal fluid (pH 3.4). These results indicate that HPMCAM might be a useful material for a duodenum-specific drug delivery system.

• 대한의용생체공학회:의공학회지
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• 제18권2호
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• pp.173-178
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• 1997

pH sensitive polymers have long been utilized as one important type among many interesting drug delivery systems. This is due to the reason of different pH environments in human organs, which requires different pH control mechanism depending upon the organs. In the present study the pH sensitivity was investigated for both pH sensitive and pH insensitive biopolymers using the diffusion effect along with the swelling effect. NMR microscopy was performed along with optical microscopy. For the analysis of diffusion effect, UMR Microscopy was perFormed to measure diffusion coefficients for various liquids such as distilled water, acetone and DMSO(dimethyl sulfoxide). Also, this technique is expected to contribute to the studies for many pH drug delivery systems.

• Biotechnology and Bioprocess Engineering:BBE
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• 제6권4호
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• pp.205-212
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• 2001

One of the important characteristics of biological systems os their ability to change im-portant properties in response to small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting models for the development of "smart" polymeric biomaterials with biomimetic properties. An important example of this is the protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis, then out of the endosome into the cytoplasm, and from there into the nucleus, We have designed a family of synthetic polymers whose compositions have been de-signed to mimic specific peptides on viral coats that facilitate endosomal escape. Our biomimetic polymers are responsive to the lowered pH whinin endosomes, leading to distruption of the en-dosomal membrane and release of important biomolecular druges such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes and degraded by lysosomal en-zymes. In this article, we review our work on the design, synthesis and action of such smart, pH-sensitive polymers.

• Macromolecular Research
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• 제16권2호
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• pp.169-177
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• 2008

This paper reports a facile synthesis of new water-soluble poly(ethylene oxide) (PEO)-based amphiphilic block copolymers showing pH sensitive phase transition behaviors. The copolymers were prepared by atom transfer radical polymerization (ATRP) of methacrylamide type of monomers carrying a sulfonamide group using a PEO-based macroinitiator and a Cu(I)Br/$Me_6TREN$ catalytic system in aqueous media. The resulting polymers were characterized by a combination of $^1H$-NMR, size exclusion chromatography, and UV/Visible spectrophotometeric analysis. The micellization of the block copolymers as a drug-loading mechanism in aqueous media using fluorescein salt was examined as a function of pH. The stable micelle formation and its loading efficacy suggest that the block copolymers can be used as precursors for drug-nanocontainers.

• 대한의용생체공학회:의공학회지
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• 제28권3호
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• pp.344-347
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• 2007

A interpenetrating polymer network (IPN) hydrogel, composed of chitosan (CS) and poly(diallydimethylammonium chloride) (PDADMAC) was prepared, which exhibited electrical sensitive behavior. The swelling behavior of the CS/PDADMAC SIPN hydrogel was studied by immersion of the gel into various pH buffer solutions, and their stimuli response in electric fields also investigated. In order to clarify the relationship between the equilibrium swelling ratio and bending behavior of the SIPN hydrogels, the state of water in the SIPN hydrogel was also investigated using differential scanning calorimetry (DSC).