• 약학회지
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• 제54권5호
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• pp.323-327
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• 2010

Translationally controlled tumor protein (TCTP) activates basophils to release histamine and causes chronic inflammation. It was also reported that TCTP significantly reduced in brain of Alzheimer's Disease and Down Syndrome as compared to normal person, suggesting that TCTP might be involved in cognitive function. We wondered whether TCTP could act as a general inducer in neurotransmitters release in brain. We, therefore, investigated the role of TCTP in PC12 cell line which expressed neuronal properties. We found that TCTP could activate JNK, and the activity was inhibited by pretreatment of dicoumarol, a JNK inhibitor. However, TCTP could not activate ERK that has known to be involved in neurotransmitter release. These suggest TCTP did not participate in neurotransmitter release from PC12 cells, and TCTP might not be a general inducer in neurotransmitter release.

• Macromolecular Research
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• 제16권5호
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• pp.429-433
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• 2008

Alginate/carboxymethyl scleroglucan (CMSG) hydrogels were suggested as a novel carrier for the controlled release of protein drugs. The drug release characteristics of alginate hydrogels were improved by CMSG addition. Scleroglucan (Sclg) was carboxymethylated using monochloroacetic acid in aqueous alkaline medium. Alginate/CMSG hydrogels were prepared by dropping the mixture solution of alginate/CMSG into calcium chloride solution. The swelling behaviors and drug release characteristics of the hydrogels were investigated in the buffers of pH 1.2 or 7.4. As the CMSG content increased in the hydrogels, the swelling ratio of the alginate/CMSG hydrogel increased rapidly in the buffer of pH 7.4. At pH 1.2, however, the swelling ratio significantly decreased compared to that at pH 7.4. According to in vitro release tests, only 15% of ovalbumin, investigated as a model protein drug, was released from the alginate/CMSG hydrogels at pH 1.2 within 6 h. At pH 7.4, however, the drug release significantly increased due to the rapid swelling of the hydrogels. The release and swelling behaviors of the hydrogels could be controlled by changing the CMSG content in the hydrogels. These results supported the use of alginate/CMSG hydrogels as a suitable carrier for the controlled release of protein drugs in a pH responsive manner.

• Biotechnology and Bioprocess Engineering:BBE
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• 제6권5호
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• pp.326-331
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• 2001

With the aim of developing of pH-sensitive controlled drug release system, a poly(Llysine) (PLL) based cationic semi-interpenetrating polymer network (semi-IPN) has been synthesized. This cationic hydrogel was designed to swell at lower pH and de-swell at higher pH and therefore be applicable for achieving regulated drug release at a specific pH range. In addition to the pH sensitivity, this hydrogel was anticipated to interact with an ionic drug, providing another means to regulate the release rate of ionic drugs. This semi-IPN hydrogel was prepared using a free-radical polymerization method and by crosslinking of the polyethylene glycol (PEG)-methacrylate polymer through the PLL network. The two polymers were penetrated with each other via interpolymer complexation to yield the semi-IPN structures. The PLL hydrogel thus prepared showed dynamic swelling/de-swelling behavior in response to pH change, and such a behavior was influenced by both the concentrations of PLL and PEG-methacrylate. Drug release from this semi-IPN hydrogel was also investigated using a model protein drug, streptokinase. Streptokinase release was found to be dependent on its ionic interaction with the PLL backbones as well as on the swelling of the semi-IPN hydrogel. These results suggest that a PLL semi-IPN hydrogel could potentially be used as a drug delivery platform to modulate drug release by pH-sensitivity and ionic interaction.

• Journal of Dairy Science and Biotechnology
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• 제23권2호
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• pp.115-123
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• 2005

Microcapsules consisting of natural, biodegradable polymers for controlled and/or sustained core release applications are needed. Physicochemical properties of whey proteins suggest that they may be suitable wall materials in developing such microcapsules. The objectives of the research were to develop water-insoluble, whey protein-based microcapsules containing a model water-soluble drug using a chemical cross-linking agent, glutaraldehyde, and to investigate core release from these capsules at simulated physiological conditions. A model water soluble drug, theophylline, was suspended in whey protein isolate (WPI) solution. The suspension was dispersed in a mixture of dichloromethane and hexane containing 1% biomedical polyurethane. Protein matrices were cross-linked with 7.5-30 ml of glutaraldehyde-saturated toluene (GAST) for 1-3 hr. Microcapsules were harvested, washed, dried and analyzed for core retention, microstructure, and core release in enzyme-free simulated gastric fluid (SGF) and simulated intestinal fluid(SIF) at $37^{\circ}C$. A method consisting of double emulsification and heat gelation was also developed to prepare water-insoluble, whey protein-based microcapsules containing anhydrous milkfat (AMF) as a model apolar core. AMF was emulsified into WPI solution (15${\sim}$30%, pH 4.5-7.2) at a proportion of 25${\sim}$50%(w/w, on dry basis). The oil-in-water emulsion was then added and dispersed into corn oil ($50^{\circ}C$) to form an O/W/O double emulsion and then heated at $85^{\circ}C$ for 20 min for gelation of whey protein wall matrix. Effects of emulsion composition and pH on core retention, microstructure, and water-solubility of microcapsules were determined. Overall results suggest that whey proteins can be used in developing microcapsules for controlled and sustained core release applications.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.385-390
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• 2000

To demonstrate the effect of formulation conditions on the controlled release of protein from poly(lactide-co-glycolide) (PLGA) microspheres for use as a parenteral drug carrier, ovalbumin (OVA) microspheres were prepared using the W/O/W multiple emulsion solvent evaporation and extraction method. Methylene chloride or ethyl acetate was applied as an organic phase and poly(vinyl alcohol) as a secondary emulsion stabilizer. Low loading efficiencies of less than 20％ were observed and the in vitro release of OVA showed a burst effect in all batches of different microspheres, followed by a gradual release over the next 6 weeks. Formulation processes affected the size and morphology, drug content, and the controlled release of OVA from PLGA microspheres.

• 한국유가공학회:학술대회논문집
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• 한국유가공기술과학회 2005년도 창립 30주년 기념 국제심포지움 - 웰빙시대의 우유.유제품의 새로운 발견
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• pp.37-61
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• 2005

미세캡슐 (microencapsulation)은 내부 물질(core material)의 방출을 제어하기 위하여 여러 천연 및 생분해성 물질이 사용된다. 유청단백질은 이러한 목적에 아주 적합한 것으로 여겨지고 있는데 이는 독특한 이화학적 특성에 기인되는 것이다. 본 연구팀은 drug이나 생리활성물질을 피복하기 위하여 cross-linking 물질로 glutaraldehyde를 사용하여 수용성 이면서 유청단백질을 근간으로 하는 미세캡슐 제조기술을 개발하였다. 또한 생리적 조건에서 이들 캡슐의 분해 및 포집물질의 방출에 대한 연구를 수행하였는데 수용성 drug으로 사용된 theophylline은 유청단백질에 잘 분산되는 것으로 확인되었다. 이 분산액은 !%의 생리활성물질인 polyurethane을 함유하는 dichloromethane과 hexane 혼합불에 잘 확산이 되었다. 미세캡슐공정에서 피복물질로 사용되는 여러 물질중에서 유청단백질은 생리적 효능이 뛰어나고 여러 물리적 작용이 있기 때문에 새로운 피복소재로써 그 효용성이 매우 높다. 지금까지의 연구결과 유청단백질을 이용한 미세캡슐의 제조는 유청단백질이 가지는 기능적 효과와 내부물질이 지니는 약리효과를 동시에 이용할 수 있다는 점에서 향후 고부가 식품 의약품 첨가물질로써 유용성이 기대된다고 하겠다.

• 약학회지
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• 제44권3호
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• pp.251-256
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• 2000

Sterically stabilized liposomes (SSL) composed of distearoylphosphatidylcholine, cholesterol, dicetylphosphate and distearoylphosphatiodylethanolamine-N-poly(ethyleneglycol) 2000 (DSPE-PEG 2000) were made by reverse phase evaporation method to prolong biological half-life and decrease toxic side effect of drug. Streptozocin (572), a water-soluble antitumor agent with short half-life, was selected as a model drug. The size of SSL was controlled by polycarbonate extrusion to 100 nm which is adequate size for long circulation in plasma. The release rate of drugs from SSL in PBS was evaluated. And the stability of STZ-containing liposomes against drug leakage into rat plasma was evaluated in order to investigate the interaction of liposome and plasma protein. Incorporation of DSPE-PEG 2000 into conventional liposomes significantly decreased the drug leakage into rat plasma.

• 대한의생명과학회지
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• 제12권4호
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• pp.443-450
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• 2006

To demonstrate their possibilities as an enhanced vaccine delivery system, protein-loaded Poly lactide glycolide copolymer (PLGA) microspheres were prepared with different physical characteristics. Ethyl acetate (EA) solvent extraction process was employed to prepare microspheres and the effects of process parameters on drug release properties were evaluated. The biodeuadability of microspheres was also evaluated by the pH change and GPC (Gel permeation chromatography). Primary IgG antibody responses in BALB/c mice were compared with protein saline solutions as negative controls and adsorbed alum suspensions as positive controls after single subcutaneous injection for in vivo studies. The microspheres showed a erosion with a highly porous structure and did not keep their spherical shape at 45 days and this result could be confirmed by GPC. In vitro release of proteinous drug showed initial burst effect in all batches of microspheres, followed by gradual release over the next 4 weeks. PLGA microspheres were degraded until 45 days and the secondary structure of OVA was not affected by the preparation method. Enzyme-linked immunosorbent assays demonstrated that the single subcutaneous administrations of OVA-loaded PLGA microspheres induced enhanced serum IgG antibody response in comparison to negative and positive controls. These results demonstrated that microspheres providing the controlled release of antigens might be useful in advanced vaccine formulations for the parenteral carrier system.

• Journal of Pharmaceutical Investigation
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• 제31권1호
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• pp.43-47
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• 2001

Sterically stabilized liposomes (SSL) have been introduced for longer circulation in blood than conventional liposomes (CL). However, there are a couple of problems in SSL preparation due to the instability of phospholipid and the degradation of drug in aqueous conditions. To solve these problems, it is necessary to go through lyophilization process. Therefore, in this study, effects of lyophilization on SSL were evaluated for physical characteristics changes upon rehydration of lyophilized SSL such as the particle size, efficiency of drug entrapment, turbidity and drug release. SSL containing streptozocin, a water-soluble anticancer drug as a model compound, were prepared with DSPC and DSPE-PEG 2000. The size was controlled to 100 nm by extrusion with polycarbonate membrane, and sucrose was used as a cryoprotectant for lyophilization at the 1:3 (lipid:sucrose) ratio. Upon rehydration of lyophilized SSL, the average size was in the range of $50{\sim}200\;nm$ which is adequate for longer circulation in blood, and the encapsulation efficiency was kept as its initial state. Rehydrated SSL were not adsorbed to rat plasma protein and revealed a similar drug release profile to that of fresh SSL before lyophilization. Therefore, lyophilization could be introduced efficiently to overcome aqueous instability problems of SSL.

• 폴리머
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• 제29권5호
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• pp.468-474
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• 2005

약물 전달체로서 캬비톨에 의해 개시된 PLGA와 PCL은 락타이드, 글라이콜라이드, 그리고 카프로락톤의 개환 중합에 의해서 합성되었다. 이들 합성고분자를 이용한 이식형 웨이퍼는 합성고분자와 모델 단백질 약물로서 소혈청알부민의 물리적 혼합 후에 성형 압축법에 의해서 간단히 제조되었다. 웨이퍼로부터 알부민의 방출량은 형광측정기를 사용하여 형광 강도에 의해서 측정되었다. 또한 웨이퍼에서 알부민의 방출거동은 콜라겐, 소장점막하조직, 폴리비닐피롤리돈, 그리고 폴리에틸렌글리콜과 같은 첨가제를 통해 조절되었다. PLGA와 PCL로만 준비된 웨이퍼에서의 알부민의 방출은 30일 동안 $10\%$ 미만의 느린 방출거동을 보였다. 그러나 첨가제를 함유한 웨이퍼는 첨가제 함량에 따라서 다양한 서방형의 방출거동을 보였다. 더욱이 콜라겐과 소장점막하조직과 같은 천연재료를 함유한 웨이퍼는 폴리비닐피롤리돈, 폴리에틸렌글리콜과 같은 합성재료를 함유한 웨이퍼보다 0차 방출의 거동을 보였다. 이러한 이식형 웨이퍼로부터 알부민의 방출은 천연재료의 첨가를 통해 쉽게 조절할 수 있음을 확인하였다.