• Biomolecules & Therapeutics
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• 제25권4호
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• pp.441-451
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• 2017

Imperatorin, a major bioactive furanocoumarin with multifunctions, can be used for treating neurodegenerative diseases. In this study, we investigated the characteristics of imperatorin transport in the brain. Experiments of the present study were designed to study imperatorin transport across the blood-brain barrier both in vivo and in vitro. In vivo study was performed in rats using single intravenous injection and in situ carotid artery perfusion technique. Conditionally immortalized rat brain capillary endothelial cells were as an in vitro model of blood-brain barrier to examine the transport mechanism of imperatorin. Brain distribution volume of imperatorin was about 6 fold greater than that of sucrose, suggesting that the transport of imperatorin was through the blood-brain barrier in physiological state. Both in vivo and in vitro imperatorin transport studies demonstrated that imperatorin could be transported in a concentration-dependent manner with high affinity. Imperatorin uptake was dependent on proton gradient in an opposite direction. It was significantly reduced by pretreatment with sodium azide. However, its uptake was not inhibited by replacing extracellular sodium with potassium or N-methylglucamine. The uptake of imperatorin was inhibited by various cationic compounds, but not inhibited by TEA, choline and organic anion substances. Transfection of plasma membrane monoamine transporter, organic cation transporter 2 and organic cation/carnitine transporter 2/1 siRNA failed to alter imperatorin transport in brain capillary endothelial cells. Especially, tramadol, clonidine and pyrilamine inhibited the uptake of [$^3H$]imperatorin competitively. Therefore, imperatorin is actively transported from blood to brain across the blood-brain barrier by passive and carrier-mediated transporter.

• 대한화학회지
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• 제50권6호
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• pp.464-470
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• 2006

약물인 덱사메타손은 효과적인 염증치료제이다. 그러나 난용성 약물로써 수용액에서 주사제로 가용화가 어렵다. 따라서 º ¿±¸에서는 ¸Þ¸손을 수용액상에서 주사제로 가용화하기 §Ø¼­ 지질로 만들어진 나노입자에 ¸Þ¸손을 봉입하여 체내투여 시 약물을 서서히 방출할 수 ´ 약물전달체를 제조하고자 ¿´´. 지질나노입자는 인지질, 콜레스테롤 ±×¸?簾? 양이온성 지질을 사용하여 자발 유화 ¿매확산법에 의해 제조하였다. ³ª노입자는 다양한 지질 종류와 지질의 함량에 따라서 봉입효율, 기 그리고 표면전하와 °°º ¹°리적 특성을 평가하였다. 기는 80~120 nm ¿´¸¸, 봉입효율은 80% 이상의 높은 효율을 보였다. 질의 지방쇄의 길이가 ±æ¼· 봉입효율은 증가하였고, 콜레스테롤의 량과 봉입효율은 반비례하였다. 나노지질입자는 양이온성 지질 없이는 형성되지 않았으며 ¾온성 지질의 ·?閻?¡ 따라서 봉입효율은 °¡하였다. 덱사메타손이 봉입된 지질나노입자는 난용성 약물을 주사제로 가용화 수 ´ 새로운 약물전달체로써의 가능성을 기대하는 바이다.

• 한국정보통신학회논문지
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• 제20권12호
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• pp.2395-2400
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• 2016

암 환자들을 대상으로 하는 항암치료법은 나노입자, 폴리머 중합체, 지질, 리포솜 등을 치료 전달체로 이용하여 항암치료를 진행하는 방법들이 주로 활발하게 사용되고 있다. 이러한 전달체는 항암 치료제를 직접 암세포로 정확하게 표적 운반하는 정확성, 정확하게 운반한 후 선택적으로 항암치료제를 방출해야하는 유출제어, 다른 일반 세포들을 약물로부터 보호하는 기능 등을 동시에 가지고 있어야 하지만, 대부분 항암약물의 독성에 기인한 부작용이 발생하고 있다. 겸형적혈구는 암세포주변 혈관세포와 멤브레인 표면에 존재하는 리셉터 사이에의 점착성이 존재하며 추가적 생화학처리 없이 암세포 주변에 표적화가 가능함을 보인다. 또한, 암세포 주변의 혈관의 구조적 변화특성은 겸형적혈구의 중합화 반응을 증가시킨다. 따라서 본 논문에서는 겸형적혈구를 이용한 새로운 항암치료법의 효과를 정량적 혈관분석 방법을 통해 제시하고자 한다.

• 대한화학회지
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• 제48권6호
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• pp.616-622
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• 2004

약물 수송체로 사용되는 리포솜은 동결 건조를 통하여 분말화 시키는 방법이 사용되어지고 있다. 리포솜 안정제로서 말토스는 동결건조된 리포솜 분말의 안정성을 향상시키고 약물 봉입률에 영향을 주는 것으로 알려져 왔다. 동결건조 전과 후의 리포솜 입자의 크기를 측정하므로서 리포솜의 안정성을 평가하였고 또한, 약물 봉입률은 모델 약물인 칼세인을 사용하여 조건에 따른 봉입양을 측정하였다. 리포솜 제조 후에 말토스를 첨가한 리포솜은 수화하는 과정에서 말토스를 첨가하여 제조한 리포솜보다 훨씬 더 안정한 것으로 확인되었다. 말토스를 첨가하지 않은 리포솜은 시간이 지남에 따라 입자의 크기가 커지는 반면, 리포솜 제조 후에 말토스를 첨가한 리포솜은 $4{\sim}37^{\circ}C$에서 30일 동안 안정하다. 또한, 말토스/지질의 물농도 비가 3과 6일 때 상대적으로 가장 높은 안정성을 보였다.

• Archives of Pharmacal Research
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• 제29권8호
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• pp.712-719
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• 2006

In this study, we prepared core-shell type nanoparticles of a poly(DL-lactide-co-glycolide) (PLGA) grafted-dextran (DexLG) copolymer with varying graft ratio of PLGA. The synthesis of the DexLG copolymer was confirmed by $^1H$ nuclear magnetic resonance (NMR) spectroscopy. The DexLG copolymer was able to form nanoparticles in water by self-aggregating process, and their particle size was around $50\;nm{\sim}300\;nm$ according to the graft ratio of PLGA. Morphological observations using a transmission electron microscope (TEM) showed that the nanoparticles of the DexLG copolymer have uniformly spherical shapes. From fluorescence probe study using pyrene as a hydrophobic probe, critical association concentration (CAC) values determined from the fluorescence excitation spectra were increased as increase of DS of PLGA. $^1H-NMR$ spectroscopy using $D_2O$ and DMSO approved that DexLG nanoparticles have core-shell structure, i.e. hydrophobic block PLGA consisted inner-core as a drug-incorporating domain and dextran consisted as a hydrated outershell. Drug release rate from DexLG nano-particles became faster in the presence of dextranase in spite of the release rate not being significantly changed at high graft ratio of PLGA. Core-shell type nanoparticles of DexLG copolymer can be used as a colonic drug carrier. In conclusion, size, morphology, and molecular structure of DexLG nanoparticles are available to consider as an oral drug targeting nanoparticles.

• 폴리머
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• 제28권4호
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• pp.335-343
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• 2004

카뮤스틴 (1,3-bis(2-chloroethy1-nitrosourea, BICNU)은 뇌종양 치료를 위하여 임상적으로 사용되는 약물로 짧은 생물학적 반감기를 가지고 있어 장기방출에 적합하지 않다. 하지만, poly(D,L-lactide-co-glycolide) (PLGA)는 벌크 분해 특성으로 인해 약물의 장기방출에 유용하며, PLGA의 유도체인 글리콜라이드 단량체는 독성이 없고 PLGA와 유사한 생분해성을 가지고 있어 BICNU의 방출조절에 이용된다. 이 실험에서 BICNU를 함유한 PLGA 웨이퍼는 일반적인 직접압축법에 의해 제조한 후 BICNU의 방출거동과 웨이펴의 분해속도를 전자주사현미경, 핵자기공명장치 그리고 젤투과크로마토그래피를 통해 관찰하였다. 또한, 글리콜라이드 단량체의 함량변화에 따른 다중층 웨이퍼를 제조하여 단일층 웨이퍼와의 방출거동을 비교하였다. 이러한 결과들로부터 BICNU를 함유한 PLGA 웨이퍼의 약물방출은 BICNU와 글리콜라이드 단량체의 함량이 증가할수록 증가하였고, 다중층 웨이퍼에서 외부층의 글리콜라이드 단량체와 BICNU가 약물방출 거동과 분해속도에 영향을 미친다는 것을 확인하였다.

• Journal of Veterinary Science
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• 제24권6호
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• pp.74.1-74.15
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• 2023

Background: Antibiotic beads are used to treat local bacterial infections by delivering high drug concentrations to infected tissue. Objectives: This study examined the elution characteristics of metronidazole from metronidazole-calcium sulfate (MCa) and metronidazole-calcium-potassium sulfate (MCaK) beads over 20 days and the antibacterial efficacy of the beads after storage. Methods: The MCa and MCaK beads were prepared by mixing 250 mg of metronidazole and 10 g of calcium sulfate hemihydrate with water and a 3% potassium sulfate solution, respectively. The beads were placed in phosphate-buffered saline for the elution study. The metronidazole eluents were determined using high-performance liquid chromatography. The microstructures were examined by scanning electron microscopy (SEM), and the antimicrobial activity was evaluated by a microbioassay. Results: For the 20-day study, the total amount of metronidazole released was greater in the MCa beads than in the MCaK beads by 6.61 ± 0.48 mg (89.11% ± 3.04%) and 4.65 ± 0.36 mg (73.11% ± 4.38%), respectively. The amounts of eluted drugs from the MCa and MCaK beads were higher than the minimum inhibitory concentration at 0.5 ㎍/mL against anaerobic bacteria at both 20 days and 14 days. SEM showed that calcium crystals on the outer surface had dissolved after elution, and thinner calcium crystals were prominent in the MCaK beads. The MCa and MCaK beads exhibited antibacterial activity after setting, followed by storage at room temperature or 4℃ for 21 days. Conclusions: The MCa beads could release more drug than the MCaK beads, but all eluted metronidazole amounts were effective in controlling bacterial infections. Both metronidazole beads could be stored at ambient temperature or in a refrigerator.

• Asian Pacific Journal of Cancer Prevention
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• 제15권1호
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• pp.49-54
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• 2014

Background: Hydrogels are a class of polymers that can absorb water or biological fluids and swell to several times their dry volume, dependent on changes in the external environment. In recent years, hydrogels and hydrogel nanocomposites have found a variety of biomedical applications, including drug delivery and cancer treatment. The incorporation of nanoparticulates into a hydrogel matrix can result in unique material characteristics such as enhanced mechanical properties, swelling response, and capability of remote controlled actuation. Materials and Methods: In this work, synthesis of hydrogel nanocomposites containing magnetic nanoparticles are studied. At first, magnetic nanoparticles ($Fe_3O_4$) with an average size 10 nm were prepared. At second approach, thermo and pH-sensitive poly (N-isopropylacrylamide -co-methacrylic acid-co-vinyl pyrrolidone) (NIPAAm-MAA-VP) were prepared. Swelling behavior of co-polymer was studied in buffer solutions with different pH values (pH=5.8, pH=7.4) at $37^{\circ}C$. Magnetic iron oxide nanoparticles ($Fe_3O_4$) and doxorubicin were incorporated into copolymer and drug loading was studied. The release of drug, carried out at different pH and temperatures. Finally, chemical composition, magnetic properties and morphology of doxorubicin-loaded magnetic hydrogel nanocomposites were analyzed by FT- IR, vibrating sample magnetometry (VSM), scanning electron microscopy (SEM). Results: The results indicated that drug loading efficiency was increased by increasing the drug ratio to polymer. Doxorubicin was released more at $40^{\circ}C$ and in acidic pH compared to that $37^{\circ}C$ and basic pH. Conclusions: This study suggested that the poly (NIPAAm-MAA-VP) magnetic hydrogel nanocomposite could be an effective carrier for targeting drug delivery systems of anti-cancer drugs due to its temperature sensitive properties.

• Journal of Pharmaceutical Investigation
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• 제25권1호
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• pp.37-46
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• 1995

The experiment was designed to investigate the sustained release dosage form of silymarin (SL) from chitosan (CS) carrier. Solid dispersed system was prepared by mixing the drug with chitosan. This solid dispersed system was cross-linked by glutaraldehyde, formaldehyde, acetaldehyde and butylaldehyde, respectively. The dissolution rates of these preparations were compared with each other in vitro. The silymarin was mired with anionic alginate gel and bead was prepared by dropping this mixture to cationic chitosan solution including calcium chloride. Chitosan encapsulated alginate bead after drying in the oven was investigated for the dissolution rate. The dissolution rate of SL-CS mixture was delayed with increase in the amounts of CS and the concentration of aldehyde. The effect on the delay of dissolution rate was in the increasing order of formaldehyde, glutaraldehyde, acetaldehyde, butylaldehyde. The dissolution rate of chitosan encapsulated alginate bead was parallel with the concentration of chitosan in diluted hydrochloric acid solution and delayed with increase in the concentration of chitosan in phosphate buffer solution.

• Journal of Microbiology and Biotechnology
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• 제29권11호
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• pp.1769-1776
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• 2019

Ethyl (S)-3-hydroxy-3-(2-thienyl) propanoate ((S)-HEES) acts as a key chiral intermediate for the blockbuster antidepressant drug duloxetine, which can be achieved via the stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoate (KEES) that contains a 3-oxoacyl structure. The sequences of the short-chain dehydrogenase/reductases from Chryseobacterium sp. CA49 were analyzed, and the putative 3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to stereoselectively catalyze the NADPH-dependent reduction to produce (S)-HEES. The reductase activity of ChKRED12 towards other substrates with 3-oxoacyl structure were confirmed with excellent stereoselectivity (>99% enantiomeric excess) in most cases. When coupled with a cofactor recycling system using glucose dehydrogenase, the ChKRED12 was able to catalyze the complete conversion of 100 g/l KEES within 12 h, yielding the enantiopure product with >99% ee, showing a remarkable potential to produce (S)-HEES.