• Genomics & Informatics
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• 제14권4호
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• pp.255-264
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• 2016

The plethora of genome sequence information of bacteria in recent times has ushered in many novel strategies for antibacterial drug discovery and facilitated medical science to take up the challenge of the increasing resistance of pathogenic bacteria to current antibiotics. In this study, we adopted subtractive genomics approach to analyze the whole genome sequence of the Fusobacterium nucleatum, a human oral pathogen having association with colorectal cancer. Our study divulged 1,499 proteins of F. nucleatum, which have no homolog's in human genome. These proteins were subjected to screening further by using the Database of Essential Genes (DEG) that resulted in the identification of 32 vitally important proteins for the bacterium. Subsequent analysis of the identified pivotal proteins, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) Automated Annotation Server (KAAS) resulted in sorting 3 key enzymes of F. nucleatum that may be good candidates as potential drug targets, since they are unique for the bacterium and absent in humans. In addition, we have demonstrated the three dimensional structure of these three proteins. Finally, determination of ligand binding sites of the 2 key proteins as well as screening for functional inhibitors that best fitted with the ligands sites were conducted to discover effective novel therapeutic compounds against F. nucleatum.

• Biomolecules & Therapeutics
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• 제6권1호
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• pp.73-81
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• 1998

Pregnant Sprague-Dawley rats were administered with Q-35 at the dose levels of 0, 30, 100 and 300 mg/kg/day by oral gavage from gestation day 17 to lactation period. Effects of the test chemical on general findings, reproductive performance of dams and development of Fl generation were examined. There were no treatment related changes in physical signs, body weight, necropsy findings, organ weights, delivery and nursing behavior. In 100 and 300 mg/fg/day treated groups, the food consumption of dams was decreased significantly during gestational day 19~21. The gestation length of 300 mg/tg/day treated group was increased significantly compared to the control group (22.3 $\pm$0.48 vs 22.0$\pm$0.39). Although the gestational length of all groups were in normal range of the rat, potential effect of the drug could not be ruled out. External anomaly of Fl fetus induced by Q-35 was not detected in any groups. There were no treaoent related changes in physical development, reflex functions, sensory functions, locomotor activity and motor coordinating activity. Estrus cycle, fertility and reproductive performance of Fl were not changed in all treated groups. There was no external abnormality related to the drug administration on the examination of F2. These results suggest that Q-35 has no adverse effect on the peri- and postnatal period in rats except the reduction of food consumption at the beginning of drug administration and the potential effect on the elongation of gestation length.

• Journal of Pharmaceutical Investigation
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• 제34권1호
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• pp.35-42
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• 2004

Ibuprofen (IBU), is a non-steroidal anti-inflammatory drug, used to treat rheumatoid arthritis, removal of fever and mild to moderate pain. Because of small dosage and very low accumulation in the body, IBU has been used to heal children's fever. However, IBU was very low solubility in a low pH and water (in water $0.03{\sim}2.5$ mg/ml). A nanoemulsion containing IBU by means of self-microemulsion drug delver system (SMEDDS) was prepared in order to enhance the solubility of IBU. The SMEDDS was composed of cosurfactant, oil and surfactant The solubility of IBU in various components such as cosurfactant, oil and surfactant was examined. $Carbitol^{\circledR}\;(386.99{\pm}20.5\;mg/ml)$ as a cosurfactant, $Labrafil^{\circledR}$　 M1944CS $(90.16{\pm}1.60mg/ml)$ as an oil and $Cremopher^{\circledR}$　 RH-40 $(239.01{\pm}2.8\;mg/ml)$ as a surfactant were used in this study for preparing SMEDDS. Optimized formulation of SMEDDS was obtained by phase diagram which express the section of nanoemulsion formation. The SMEDDS containing IBU had higher dissolution rate than conventional IBU sirups. Thus the SMEDDS was a potential candidate of stable conventional and effective oral dosage form for IBU.

• 폴리머
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• 제31권4호
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• pp.329-334
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• 2007

경구를 통한 약물전달시스템 중 하나인 삼투압을 이용한 삼투정 펠렛의 제조는 타블렛 제형이 갖는 제조 공정상의 복잡함과, 생산비용 등의 문제들을 줄이고자 시도되었다. 삼투정 펠렛은 수팽윤성 시드층과 약물층 그리고 반투막층으로 구성되었으며, 이중에서 반투막층은 약물의 방출을 조절하는 중요한 역할을 한다. 이번 연구에서는 반투막층으로 사용되는 Eudragit RL과 RS의 비에 대한 영향과 코팅두께에 따른 약물방출 거동을 확인하고자 하였다. 모델약물인 니페디핀을 포함한 삼투정 펠렛의 제조는 유동층 코팅기를 이용하여 제조하였으며, 비교적 높은 코팅 수율과 $1300{\sim}1500\;{\mu}m$ 크기의 펠렛을 얻었다. 얻어진 펠렛의 Eudragit RL과 RS의 비에 따른 약물방출 거동을 보면, Eudragit RL의 비가 증가할수록 약물의 방출은 증가함을 확인하였다. 이는 Eudragit RL이 RS보다 친수성 4차 암모늄 그룹을 더 많이 갖기 때문이다. 또한 반투막의 코팅 두께가 증가할수록 약물의 방출이 지연됨을 확인하였다. 반투막과 모델약물의 pH의 변화에 대한 약물방출의 영향을 알아보기 위하여 pH 1.2, 6.5, 6.8, 7.2의 서로 다른 pH에서 실험을 실시하였으며, pH의 변화에 관계없이 약물방출이 안정적으로 일어남을 확인하였다. 이번 실험을 통하여 삼투정 펠렛의 약물방출은 펠렛의 반투막 조성과 코팅두께에 의존함을 확인하였다.

• Journal of Pharmaceutical Investigation
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• 제40권2호
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• pp.85-90
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• 2010

Docetaxel-loaded liposomes were prepared by emulsion-solvent evaporation method, then coated with chitosan at room temperature and lyophilized. This system was designed in order to improve solubility and stability of docetaxel in the GI tract for oral drug delivery. The solubilizing effect of some frequently used solubilizers and/or liposome was determined. Among the results docetaxel-loaded liposomes prepared with 0.5% TPGS as a solubilizer showed 100-fold higher solubility than docetaxel. In a stability test, mean particle size of different liposome formulations was measured by a particle size analyzer in simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). The particle size of uncoated liposomes was significantly increased compared with that of chitosan-coated liposomes in SGF, however, there was no significant difference between coated and uncoated liposome in SIF. It is evident that chitosan-coated liposomes were more stable in GI conditions. The release characteristics of docetaxel-loaded liposomes were also investigated in three buffer solutions (pH 1.2, 4.0, 6.8). Docetaxel release did not occur in pH 1.2 for 4 hrs. However, in pH 4.0 and 6.8 conditions, docetaxel was gradually released over 24 hrs as a sustained release. It seems that aggregation and precipitation of particles by electrostatic interaction might protect docetaxel from being released. In Conclusion, the results from this study show that the chitosan-coated liposomes may be useful in enhancing solubility and GI stability of docetaxel.

• 폴리머
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• 제34권6호
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• pp.527-533
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• 2010

Pioglitazone을 봉입한 poly(lactide-co-glycolide)(PLGA) 나노입자를 emulsion-evaporation 방법을 이용하여 제조하여 최적의 나노입자와 봉입률을 조절하였다. 제조된 나노입자의 크기는 125~170 nm이었으며 30% pioglitazone이 봉입된 나노입자(3% PVA)의 봉입률은 85% 이상이었다. 이러한 나노입자들은 40일 동안 일정하게 용출이 되었다. 당뇨병 모델을 이용한 동물실험에서 글루코오스 농도를 저하시켰을 뿐만 아니라, 조직검사에서는 낮은 독성을 가지고 있는 것을 확인하였다. 이러한 결과는 pioglitazone 경구투여를 위한 약물전달을 위한 운반체로 사용될 수 있음을 확인하였다.

• Korean Chemical Engineering Research
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• 제43권2호
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• pp.299-304
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• 2005

음이온 하이드로젤은 그들이 가지고 있는 pH 감응성 팽윤거동 때문에 단백질 약물의 경구투여용 전달물질로써 많은 주목을 받고 있다. 본 연구에서는 음이온 하이드로젤의 pH 변화에 따른 용매의 침투 메커니즘을 규명하기 위하여 methacrylic acid와 2-methacryloxyehtyl glucoside를 공중합하여 P(MAA-co-MEG) 하이드로젤을 합성한 후 pH 변화에 따른 하이드로젤의 동적 팽윤거동을 관찰하였다. 용매의 침투 메커니즘이 Fickian 또는 non-Fickian 인지를 설명할 수 있는 특성지수 n을 $M_t/M_{\infty}=kt^n$ 관계식으로부터 계산하였다. 하이드로젤에 대한 용매의 침투 메커니즘은 주위 pH의 영향을 많이 받았으며, 젤의 $pK_a$ 보다 높은 pH인 7.0에서는 침투 메커니즘이 상대적으로 고분자사슬의 이완에 의한 지배를 많이 받는다는 것을 알 수 있었다. 한편, pH 7.0에서 고분자 이완에 의한 용매의 침투 메커니즘은 하이드로젤에 존재하는 카르복실산의 이온화에 기인한 것임을 ATR-FTIR 분광분석을 이용하여 확인하였다.

• Biomaterials and Biomechanics in Bioengineering
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• 제3권3호
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• pp.141-155
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• 2016

Two-dimensional (2D) cell culture and in vivo cancer model systems have been used to understand cancer biology and develop drug delivery systems for cancer therapy. Although cell culture and in vivo model studies have provided critical contribution about disease mechanism, these models present important problems. 2D tissue culture models lack of three dimensional (3D) structure, while animal models are expensive, time consuming, and inadequate to reflect human tumor biology. Up to the present, scaffolds and 3D matrices have been used for many different clinical applications in regenerative medicine such as heart valves, corneal implants and artificial cartilage. While tissue engineering has focused on clinical applications in regenerative medicine, scaffolds can be used in in vitro tumor models to better understand tumor relapse and metastasis. Because 3D in vitro models can partially mimic the tumor microenvironment as follows. This review focuses on different scaffold production techniques and polymer types for tumor model applications in cancer tissue engineering and reports recent studies about in vitro 3D polymeric tumor models including breast, ewing sarcoma, pancreas, oral, prostate and brain cancers.

• Journal of Periodontal and Implant Science
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• 제43권6호
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• pp.251-261
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• 2013

A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7435-7439
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• 2015

A failure of a cell to self destruct has long been associated with cancer progression and development. The fact that tumour cells may not instigate cell arrest or activate cell death mechanisms upon cancer drug delivery is a major concern. Autophagy is a mechanism whereby cell material can be engulfed and digested while apoptosis is a self-killing mechanism, both capable of hindering multiplication after cell injury. In particular situations, autophagy and apoptosis seem to co-exist simultaneously or interdependently with the aid of mutual proteins. This review covers roles of microRNAs and chemopreventive agents and makes an attempt at outlining possible partnerships in maximizing cancer cell death with minimal normal cell damage.