• Journal of Pharmaceutical Investigation
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• 제21권2호
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• pp.91-95
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• 1991

Polyethylene glycol, polypropylene glycol and block copolymer of ethylene glycol and propylene glycol were crosslinked by triisocyanate to form water swellable, rubbery polymer. The equilibrium swelling of the hydrogels ranged from 3% to 60% according to the hydrophobic-hydrophilic properties of the prepolymers. Model drugs, sodium salicylate and prednisolone were incorporated in the polymer matrices by swelling loading. Physical properties of the drugs affected the drug release mechanisms due to the change in the swelling behaviors of the polymeric devices. Zero order release was observed in the case of relatively hydrophobic polymer matrices.

• Journal of Pharmaceutical Investigation
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• 제21권4호
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• pp.237-245
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• 1991

Matrix type silicone rubber devices were designed for long-term implantable drug delivery system. Release controlling agents (RCA), i.e., polypropylene glycol, polyethylene glycol, were employed to control drug release from the devices. The release rate of drug from RCA dispersed silicone matrices was mainly dependent on hydrophilicity-hydrophobicity of drug and RCA. In the case of hydrophilic drug, the release from the RCA dispersed matrix was regulated by swelling kinetics. Especially when the relatively hydrophobic polypropylene glycol was used, swelling control mechanism induced zero-order release kinetics. Whereas, the release of hydrophobic drug was resulted from partition mechanism. The effect of RCA was to increase drug diffusivity.

• 약학회지
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• 제42권2호
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• pp.196-204
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• 1998

The blood-brain barrier (BBB) of rats was modificated opening reversibly by infusing a hyperosmotic solution of arabinose (1.6 molal) into the right external carotid artery. Pre vious studies demonstrated that permeability was increased maxmmally in the first 15 min and remained slightly elevated at 1 hr. As control reference, saline was used. In the present study, to evaluate the effects of osmotic BBB opening on the BBB trasport according to hydrophilic or hydrophobic characteristics of drugs. And the differences of the uptakes of these compounds to right (treated osmotic opening) and left (untreated) hemispheres in same rats were compared each other following injection of 8 mCi per rat of $^{99m}Tc$-ethylene triamine pentaacetic acid (DTPA) as hydrophilic drug or 5mg/kg of phenytoin as hydrophobic drug mto the right external carotid artery of rats between two groups (1.6 molal arabinose vs saline). The uptakes of $^{99m}Tc$-DTPA and phenytoin in the right cerebral hemispheres were increased to about thirty three times and twice rather than those in the left cerebral heimspheres, respectively. And PAs (permeability X capillary surface area) were also increased from a control mean of 2.11${\times}10^{-4}$ (Untreated) to 6.98${\times}10^{-3}\;sec^{-1}$ (treated osmotic opening for $^{99m}Tc$-DTPA and 0.29 to 0.17 $sec^{-1}$ for phenytoin, respectively. From the results of present study, it is noted that osmotic opening of BBB is more effective in the brain delivery of hydrophilic drugs rather than that of hydrophobic drugs.

• Journal of Pharmaceutical Investigation
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• 제41권2호
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• pp.95-102
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• 2011

An amphiphilic cationic branched methoxy poly (ethylene glycol)-branched polyethylenimine - poly(L-phenylalanine) (mPEG-bPEI-pPhe) block copolymer was successfully synthesized by ring-opening polymerization (ROP) of N-carboxyanhydride of L-phenylalanine (Phe-NCA) with mPEG-bPEI for the preparation of more stable polyelectrolyte complex (PEC) included a hydrophobic interaction. mPEG-bPEI was firstly prepared by the coupling of mPEG and bPEI using hexamethylene diisocyanate (HMDI). The structural properties of mPEG-bPEI-pPhe copolymers were confirmed by $^1H$ NMR. The copolymers exhibited a self-assemble behavior in water above critical aggregate concentration (CAC) in the range of 0.01-0.14 g/L. The CAC of copolymers obviously depended on the hydrophobic block content in the copolymers (the value decreased with the increase of the pPhe block content). The cationic copolymers have the ability to form multi-interaction complex (MIC) with bovine serum albumin (BSA) and plasmid DNA through multi-interaction (electrostatic and hydrophobic interaction). The physicochemical characterization of the complex was carried out by the measurement of zeta potential and particle size. Their zeta-potentials were positive (approximately +10 mV) and their sizes decreased with increasing pPhe contents in the copolymers (PPF/BSA wt% ratio = 2). The complex showed good stability at high ionic strength. Therefore, mPEG-bPEI-pPhe block copolymer was considered as a potential material to enhance the stability of complex including biotherapuetic drugs.

• Macromolecular Research
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• 제11권1호
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• pp.2-8
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• 2003

The self-assembly of polymers can lead to supramolecular systems and is related to the their functions of material and life sciences. In this article, self-assembly of Langmuir-Blodgett (LB) films, polymer micelles, and polymeric nanoparticles, and their biomedical applications are described. LB surfaces with a well-ordered and layered structure adhered more cells including platelet, hepatocyte, and fibroblast than the cast surfaces with microphase-separated domains. Extensive morphologic changes were observed in LB surface-adhered cells compared to the cast films. Amphiphilic block copolymers, consisting of poly(${\gamma}$-benzyl L-glutamate) (PBLG) as the hydrophobic part and poly(ethylene oxide) (PEO) [or poly(N-isopropylacrylamide) (PNIPAAm)] as the hydrophilic one, can self-assemble in water to form nanoparticles presumed to be composed of the hydrophilic shell and hydrophobic core. The release characteristics of hydrophobic drugs from these polymeric nanoparticles were dependent on the drug loading contents and chain length of the hydrophobic part of the copolymers. Achiral hydrophobic merocyanine dyes (MDs) were self-assembled in copolymeric nanoparticles, which provided a chiral microenvironment as red-shifted aggregates, and the circular dichroism (CD) of MD was induced in the self-assembled copolymeric nanoparticles.

• Journal of Photoscience
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• 제12권1호
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• pp.25-32
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• 2005

Binding of N-Alkyl phenothiazines (NAP) to bovine serum albumin (BSA) was studied by spectroscopic methods.It was found that the phenothiazine ring common to all drugs makes major contribution to interaction. However, the nature of alkylamino group at position 10 influences the protein binding significantly. Stern-Volmer plots indicated the presence of static component in the quenching mechanism. The high magnitude of rate constant of quenching indicated that the process of energy transfer occurs by intermolecular interaction and thus the drug-binding site is in close proximity to tryptophan residues of BSA. Binding studies in presence of hydrophobic probe, 8-anilino-1-naphthalein-sulphonic acid showed that there is hydrophobic interaction between drug and the probe and they do not share common sites in BSA. Thermodynamic parameters obtained from data at different temperatures showed that the binding of NAP to BSA predominantly involve hydrophobic forces. The effects of some cations and anions common ions were investigated on NAP-BSA interactions. The CD spectrum of BSA in presence of drug showedthat binding of drug leads to change in the helicity of the protein.

• KSBB Journal
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• 제22권4호
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• pp.213-217
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• 2007

첨가제가 단백질 약물 방출 속도 및 약물 제제 제조 및 구조에 미치는 영향을 고찰하였다. 친수성 첨가제인 D-sorbitol의 경우 친유성 첨가제보다 단백질 약물 방출 속도를 감소시킬 수 있었으며 최적의 농도는 3% (w/v)로 나타났다. 또한 제제 제조시 점도를 낮게 유지할 뿐 아니라 상분리 없는 균일한 pluronic 용액상태를 유지하여 약물이 첨가될 경우에 균일한 약물제제를 만들 수 있었다. 한편 D-sorbitol은 pluronic 수용액의 CMC를 낮추고 마이셀 표면에 작용하여 구조를 강화하는 역할을 수행하는 것으로 보인다. 따라서 pluronic 제제에 D-sorbitol을 첨가하여 단백질 약물의 안정성을 향상시키고 효과적인 약물전달 시스템을 설계할 수 있었다.

• Journal of Pharmaceutical Investigation
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• 제12권4호
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• pp.145-152
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• 1982

Data from IR spectroscopy and X-ray diffractometry were used for the characterization of sulpiride polyethylene glycol coprecipitates related with polymorphism of sulpiride. Sulpiride Form II transformed to Form I during coprecipitating with polyethylene glycol and the transformation rate is increased in proportion to molecular size of polyethylene glycol and the content of polyethylene glycol in coprecipitate.

• 공업화학
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• 제28권4호
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• pp.404-409
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• 2017

천연고분자 키토산은 생체적합하고 생분해성의 특성뿐만 아니라 항암, 항균, 콜레스테롤 저하 등의 다양한 생체활성을 갖고 있어 의료용 분야에서 많이 응용되고 있다. 현재 키토산을 약물전달시스템에 응용한 다양한 약물이 담지 된 키토산 나노입자를 개발하여 질병을 치료할 수 있는 연구가 활발히 진행 중에 있다. 키토산에 존재하는 free 아민($-NH_2$) 그룹은 다양한 소수성기를 물리적 화학적 개질을 통해 결합이 가능하며 소수성기가 도입된 키토산은 물에 분산시 자기회합에 의한 shell-core 나노입자를 형성하고 core 부분에 다양한 난용성 약물을 담지하여 물에 대한 용해도를 증가시킬 수 있으며, 단백질, 항암제, 백신 등의 다양한 약물을 담지하여 기존 약물의 부작용을 최소화하여 치료효과를 극대화할 수 있다. 또한, 키토산에 도입된 소수성기에 따라 입자의 크기 및 방출 속도를 제어할 수 있어 다양한 의료용 분야에 응용이 가능하다. 본 총설에서는 다양한 소수성기가 도입된 키토산 나노입자의 제조 및 특성과 특성에 따른 약물전달시스템의 응용성에 관하여 논의 하고자 한다.

• Journal of Pharmaceutical Investigation
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• 제30권1호
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• pp.33-37
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• 2000

One of the methods to increase the solubility of a drug is to use complexation with a cyclodextrin. Due to the hydrophobic nature of the interior cavity of the cyclodextrin, it has been known that undissociated lipophilic drugs can be included within the cyclodextrin by hydrophobic interaction. Recently, inclusion of hydrophilic or dissociated form of a drug has been investigated. In this study, the synergism of pH and complexation with $hydroxypropy-{\beta}-cyclodextrin\;(HP\;{\beta}\;CD)$ to increase the solubility of two oxicam derivatives was investigated. In addition, the effect of partition coefficient of dissociated and undissociated form of the drug on the extent of complexation with HP ${\beta}$ CD was studied. The solubility was measured by equilibrium solubility method. The solubility of tenoxicam and piroxicam increased exponentially with an increase in solution pH above the pKa of the drug in the presence and absence of HP ${\beta}$ CD. The solubility of the drugs increased linearly as a function of HP ${\beta}CD$ concentration at fixed pH. Although the stability constant of ionized species is less than that of the unionized species, the concentration of the ionized drug complex is greater than that of the unionized drug complex due to higher concentration of ionized species at pH 7.3.