• Journal of Microbiology and Biotechnology
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• 제29권2호
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• pp.200-208
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• 2019

Probiotics show low cell viability after oral administration because they have difficulty surviving in the stomach due to low pH and enzymes. For the oral delivery of probiotics, developing a formula that protects the probiotic bacteria from gastric acidity while providing living cells is mandatory. In this study, we developed tablets using a new pH-sensitive phthalyl inulin (PI) to protect probiotics from gastric conditions and investigated the effects of different compression forces on cell survival. We made three different tablets under different compression forces and measured survivability, disintegration time, and kinetics in simulated gastric-intestinal fluid. During tableting, there were no significant differences in probiotic viability among the different compression forces although disintegration time was affected by the compression force. A higher compression force resulted in higher viability in simulated gastric fluid. The swelling degree of the PI tablets in simulated intestinal fluid was higher than that of the tablets in simulated gastric fluid due to the pH sensitivity of the PI. The probiotic viability formulated in the tablets was also higher in acidic gastric conditions than that for probiotics in solution. Rapid release of the probiotics from the tablet occurred in the simulated intestinal fluid due to the pH sensitivity. After 6 months of refrigeration, the viability of the PI probiotics was kept. Overall, this is the first study to show the pH-sensitive properties of PI and one that may be useful for oral delivery of the probiotics.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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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.

• 한국고분자학회:학술대회논문집
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• 한국고분자학회 2006년도 IUPAC International Symposium on Advanced Polymers for Emerging Technologies
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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.

• Bulletin of the Korean Chemical Society
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• 제19권6호
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• pp.645-649
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• 1998

In order to develop pH-sensitive liposomes that are stable in plasma, liposomes containing membrane-spanning bipolar amphiphiles as protonatable components were studied. Sonicated small unilamellar liposomes composed of dioleoylphosphatidylethanol amine (DOPE), dioleoylphosphatidylcholine (DOPC) and bis(6-hemisuccinyloxyhexyl) fumarate (BHF) in a 3 : 1 : 1 molar ratio are stable at neutral pH, but destabilized at weakly acidic pH with 50% leakage of entrapped materials at about pH 5.5. The liposomes are relatively stable in plasma such that only a few percent entrapped calcein was released in 50% plasma within 1.5 h incubation at 37 ℃, while about 10% entrapped calcein was released from sonicated liposomes composed of DOPE, DOPC, and oleic acid (OA) in a 3 : 1 : 1 molar ratio under the identical conditions. The aqueous contents mixing and lipid components mixing experiments suggest that the protonation of BHF may induce fusion between the liposomes, followed by the release of the entrapped materials.

• Carbon letters
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• 제10권1호
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• pp.33-37
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• 2009

Activated carbon (AC) is one of the most effective adsorbents for organic compounds because of their extended surface area, high adsorption capacity, microporous structure and special surface reactivity. The composites of pH-sensitive hydrogel and activated carbon were prepared in order to improve the loading capacity of drug. The pH-sensitive hydrogel matrix swelled well in the basic condition to release the drug loaded in AC. The release of drug was controlled depending on both the pH due to the ionization of the carboxylic acid group and the AC due to the surface properties.

• 센서학회지
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• 제21권3호
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• pp.186-191
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• 2012

In this paper, we present a pH measurement method that uses a microcantilever-array-based biosensor system. It is composed of microcantilever array, liquid cell, micro syringe pump, laser diode array, position sensitive detector, data acquisition device, and data processing software. Four microcantilevers are functionalized with pH-sensitive MHA(mercaptohexadecanoic acid) as a probe, while three microcantilevers are functionalized with HDT(hexadecane thiol) as reference. We prepare PBS(phosphate buffered saline) solutions of different pH and inject them into the liquid cell with a predefined volumetric speed at regular time intervals. The functionalized mircocantilevers in the liquid cell deflect as a self-assembled monolayer on the microcantilever binds with probe molecules in the solution. The difference in deflection between the MHA-covered probe microcantilever and the HDT-covered reference microcantilever was used to compensate for thermal drift. The deflection difference clearly increases with increasing pH in the solution. It was shown that when the pH values of the PBS solutions are high, there were large variations in the deflection of microcantilevers, whereas there were small variations for low pH value. The experimental results show that the microcantilever array functionalized with MHA and HDT can detect pH value with good repeatability.

• Asian-Australasian Journal of Animal Sciences
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• 제18권9호
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• pp.1336-1342
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• 2005

The present research work was conducted to evaluate the beneficial effects as well as the safety aspects of lactobacilli as probiotic. Lactobacilli were isolated from poultry faecal samples, feed samples and from some known preparations procured from poultry feed manufacturers. L. acidophilus and L. sporogenes were tested for the antibacterial activity against four poultry pathogens viz. Escherichia coli, Salmonella spp., Proteus spp. and Pseudomonas aeruginosa. Cell free supernatant (CFS) of L. acidophilus exhibited significantly higher antibacterial activity against Salmonella spp. at original pH (4.50${\pm}$0.02). At the adjusted pH (6.50${\pm}$0.02) significantly higher antibacterial activity was recorded against indicator organism except for P. aeruginosa. Likewise, L. sporogenes exhibited similar antibacterial activity at original as well as adjusted pH except for E. coli. Antibacterial activity against E. coli was significantly higher at adjusted pH than at original pH of CFS. The competitive exclusion of E. coli by lactobacilli over the intestinal epithelial cells (IEC) was checked. L. acidophilus strain I, which was of poultry origin, exhibited maximum attachment over IEC as compared to other three strains of non-poultry origin viz. L. acidophilus strain II, L. sporogenes strain I and II. Overall, L. acidophilus exhibited higher competitive exclusion as compared to L. sporogenes. All the lactobacilli of poultry origin were most sensitive to penicillin G, amoxycillin, ampicillin and chloramphenicol, least sensitive to sulphamethizole, ciprofloxacin, neomycin, norfloxacin and pefloxacin and resistant to metronidazole and nalidixic acid. The isolates from probiotic preparations were most sensitive to ampicillin, amoxycillin and tetracycline, least sensitive to sulphamethizole, norfloxacin, neomycin and ceftriazone and resistant to nalidixic acid and metronidazole. Eight of the multiple drug resistant lactobacilli isolates were studied for the presence of plasmids. Plasmids could be extracted from six isolates of lactobacilli. These plasmids could be responsible for bacteriocin production or for antibiotic resistance of the strains. The lactobacilli need further studies regarding their safety for use in the probiotic preparations.

• 폴리머
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• 제25권2호
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• pp.186-198
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• 2001

pH와 온도에 민감한 N-isopropylacrylamide (NIPAAm)계 공중합체인 poly(NIPAAm-co-AAc), Poly(NIPAAm-co-AAm-GAc), 및 poly(NIPAAm-co-AMPS)를 산성 공단량체의 조성비를 달리하여 자유라디칼 중합법에 의해 제조하였다. 합성된 공중합체들의 하한임계용액온도 거동(LCST)에 대한 pH와 공단량체의 구조 및 함량변화 효과를 열광학분석기 (TOA)를 이용하여 측정한 흐림점으로부터 결정하였다. Poly(NIPA.Am-co-AAc) 수용액의 상전이온도(T$^{p}$ )는 공중합체내 AAc의 카르복실기가 이온화될수록, 보다 높은 값을 나타내었는데, 이와 같은 현상은 이온화된 상태에서 공중합체내 이온기들간의 정전기적 반발력이 보다 친수성을 나타나게 한 원인이 되었다. 반면에, 2-acrylamido glycolic acid (AAmGAc)가 공중합체에 도입된 경우, pH 3보다 낮은 pH에서는 T$^{p}$ 의 변화가 거의 없었지만, pH 3에서 5까지는 T$^{p}$ 가 매우 급격히 증가하였다가 pH 6이상에서는 공중합체의 T$^{p}$ 가 ionic screen effect에 의해 pH 3에서 pH 5일 때보다 오히려 더 낮아졌다. 또한 이 같은 ionic screen effect는 강산성 공단량체로 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS)가 도입된 공중합체 의 경우에서도 관찰되었다.

• 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.

• Archives of Pharmacal Research
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• 제28권8호
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• pp.983-987
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• 2005

Hydrogels composed of glycidyl methacrylate dextran (GMD) and poly(acrylic acid, PM) were prepared by UV irradiation method for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate to dextran in the presence of 4-(N,N-dimethylamino)pyridine. GMD was photo-polymerized by ammonium peroxydisulfate as initiating system in phosphate­buffered solution (0.1 M, pH 7.4). And then, acrylic acid monomer was added and subsequently heat-polymerized by 2,2'-azobisisobutyronitrile as an initiator. The hydrogels exhibited high swelling ratio (about 20) at $37^{\circ}C$, and showed a pH-dependent swelling behavior. In addition, the swelling ratio of the hydrogel was remarkably enhanced to about 45 times in the presence of dextranase at pH 7.4. The swelling-deswelling behavior proceeded reversibly for the GMD/PM hydrogels between pH 2 and pH 7.4. Release of 5-aminosalicylic acid from the GMD/PAA hydrogels was evaluated in simulated gastrointestinal pH fluids in the absence or presence of dextranase. We concluded that the hydrogels prepared could be used as a dual-sensitive drug carrier for sequential release in gastrointestinal tract.