• Biomolecules & Therapeutics
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• v.25 no.4
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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.

• Bulletin of the Korean Chemical Society
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• v.31 no.12
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• pp.3740-3744
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• 2010

A typically designed 'Peptide Lego' has two distinct surfaces: a hydrophilic side that contains the complete charge distribution and a hydrophobic side. In this article, we describe the fabrication of a unique lego-type peptide with the AEAEYAKAK sequence. The novel peptide with double amphiphilic surfaces is different from typical peptides due to special arrangement of the residues. The results of CD, FT-IR, AFM and DLS demonstrate that the peptide with the random coil characteristic was able to form stable nanostructures that were mediated by non-covalent interactions in an aqueous solution. The data further indicated that despite its different structure, the peptide was able to undergo self-assembly similar to a typical peptide. In addition, the use of hydrophobic pyrene as a model allowed the peptide to provide a new type of potential nanomaterial for drug delivery. These efforts collectively open up a new direction in the fabrication of nanomaterials that are more perfect and versatile.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2765-2770
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• 2011

Organic dye-doped glasses, viz., ruthenium (II) tris(4,7'-diphenyl-1,10'-phenanthroline) $[Ru(dpp)_3]^{2+}$ incorporated into thin silica xerogel films produced by the sol-gel method, were prepared and their $O_2$ quenching properties investigated as a function of the $[Ru(dpp)_3]^{2+}$ concentration (3-400 ${\mu}M$) within the xerogel. The ratio of the luminescence from the $[Ru(dpp)_3]^{2+}$-doped films in the presence of $N_2$ and $O_2$ ($I_{N2}/I_{O2}$) was used to describe the film sensitivity to $O_2$ quenching. ($I_{N2}/I_{O2}$ changed three-fold over the $[Ru(dpp)_3]^{2+}$ concentration range. Time-resolved intensity decay studies showed that there are two discrete $[Ru(dpp)_3]^{2+}$ populations within the xerogels (${\tau}_1$ ~ 300 ns; ${\tau}_2$ ~ 3000 ns) whose relative fraction changes as the $[Ru(dpp)_3]^{2+}$ concentration changes. The increased $O_2$ sensitivity that is observed at the higher $[Ru(dpp)_3]^{2+}$ concentrations is a manifestation of a greater fraction of the 3000 ns $[Ru(dpp)_3]^{2+}$ species (more susceptible to $O_2$ quenching). A model is presented to describe the observed response characteristics resulting from $[Ru(dpp)_3]^{2+}$ distribution within the xerogel.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.648-658
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• 2017

7-O-Succinyl macrolactin A (SMA) exerts several pharmacological effects including anti-bacterial, anti-inflammation, and anti-cancer activities. Recently, SMA has been extensively evaluated as an anti-cancer drug. Thus, the objectives of the present study were to characterise the pharmacokinetics of SMA via both non-compartmental and compartmental analysis in mice, rats, and dogs, and to derive an appropriate first-in-man dose based on allometric scaling of the animal data. The time courses of plasma SMA concentrations after intravenous administration to rats and dogs were analysed retrospectively, as were data collected after intraperitoneal SMA injection in mice. Pharmacokinetic parameters were estimated via both noncompartmental and compartmental analysis, and were correlated with body weight and/or the potential maximum life-span. The clearance and distribution volume of SMA in humans were predicted, and a first-in-man dose proposed. A two-compartment model best described the time courses of SMA plasma concentrations after a saturation elimination process was applied to fit the dataset obtained from rats. Incorporation of the maximum potential life-span during allometric scaling was required to improve the estimation of human clearance. The SMA clearance and the distribution volume in the steady state, in a 70-kg adult male, were estimated to be 30.6 L/h and 19.5 L, respectively. To meet the area under the curve (AUC) required for anti-tumour activity, a dose of 100 mg (~1.5 mg/kg) was finally proposed as the first dose for a 70-kg human. Although toxicological profiles derived from non-clinical studies must be considered before any final decision is made, our work will facilitate clinical studies on SMA.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.13 no.2
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• pp.112-139
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• 2000

I examined and referred to literatures of every generations on the nicknames, causes, herb medications and acupucture treatments of ptosis(上胞下垂). And then the results were obtained as follows. We've compared and analyzed Occidental and Oriental medical causes, symptoms and treatments of Primary trigeminal neuralgia and wanted to get better effects by a cooperative analysis. So the examination and analysis of the recent treatment tendency and reference bibliography show the following results. 1. Trigeminal neuralgia is nerve systematic disease appearing in the distribution scope of trigeminal nerve. It's characterized by extreme pain accompanying with a repeated and simultaneous fit from several seconds to 1-2 minutes. 2. Though there are many hypothesis on the trigeminal neuralgia, but now many doctors agree that when trigeminal nerve is under the local out of sheath conditions resulting from receiving a chronic stimulus, and the nucleus of trigeminal nerve fire, owing to decrease of pain control function and abnormal occurrence of action potential, it would be appeared. 3. The Oriental medical name of trigeminal neuralgia is generally Dootong, Doopoong, Myuntong, Pyundootong, Pyundoopoong, and Myuntong is the nearest in Occidental medicine. 4. The Oriental medical cause of trigeminal neuralgia is usually divided into Wekam and Naesang. The first one is caused by Poonghan, Poongyul, Damhwa and wicked energy enter into the body, the mechanical energy is obstructed and can't move any more, so the pain appears by them. The other cause is the hurt by emotion. And it would be loss of the transportain of liver and obstructed, so result into Kanwulhwahwa, Kanpoongnaedong and the pain appears. 5. There are two methods of curing trigeminal neuralgia. As a medication, primary method is prescribing Carbamazepine and the second is using Phenytoin or Baclofen. And as a operation, Drug injection of trigeminal nerve, Amputation of branches of trigeminal nerve, Retrogasserian glycerol rhizotomy, Radiofrequency gangliolysis, Neurovascular decompression can be used. 6. There are several herb medicines for Trigeminal neuralgia. First, Chungung is good for Hwaejeetong, Keopoongjedam, Hwalhyuljeetong. Second, Jeongal, Jiryong, Okong is used for Sikpoonghekyung, Tongkyungjeetong. Third, Baekjee, Sesin, Cheonma, Manhyungja is efficacious in Sinonhepyo. Sanpoongjeetong. Fourth, for falling of liver's Wulhwa, Yongdamcho, Hyungge, Kukwha can be used. And also Saengjihwang, Hwangkm is good for going down the fever of Yangmyungwiyul and finally, Baekkangjam. Moryu can be effective for Jaumjamyang, Haekyungjitong. The other medicines can be used as assistant analgesics, and it also efficacious. 7. Generally the points of pain on the face and the points of Soyangkyung and Yangmyungkyung is used for Acupuntual therapy, because the two meridians passed on the face. Hakwan. Sabaek, Kwanryo, Keoryo, Hyubkeo, Taeyang, Jeechang, Younghyang, Eoyo, Chanjuk. Yangbaek. Sajukkong. Dooyoo, Kwangsangjum, Sengjang, Poongjee is used for taking near point and Joksamlee, Naejung, Habkok is used for taking distant point. 8. Dansam or Danggui injection which have a effect for Hwalhyulhwaeo, Sokyunghwalak and Vit B1, Vit B2, Vit B12, $2\%$ Hydrochloroprocaine, $1\%$ Lidocaine injection to pain point for local analgesics had so good effect. And external application and moxibustion are used for another treatment. 9. It proved that through mouse model, both Herb medication group and Drug medication group are efficacious for trigeminal neuralgia similarly and also the cooperative medication group shows more effective result than the only drug medication group.

• Polymer(Korea)
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• v.31 no.3
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• pp.215-220
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• 2007

The control of the surface energy by electrohydrodynamic force provides electrospraying with various potential advantages such as simple particle size control, mono-dispersity, high recovery, and mild processing conditions. The advantages are quite helpful to improve the stability of protein drug and control its release. Herein, the nano-encapsulation of protein drugs using electrospraying was investigated. Albumin as a model protein was processed using uniaxial and co-axial electrospraying, and chitosan, polycaporlactone (PCL), and poly (ethylene glycol) (PEG) were used as encapsulation materials. The major processing parameters such as the conductivity of spraying liquids, flow rate, the distance of electrical potential gradient, etc were measured to obtain the maximum efficiency. In the chitosan systems, mean particles size decreases as flow rate and the distance between nozzle and the collecting part decreases. In the uniaxial technique of the PCL systems, mean particles size decreases as flow rate decreases. In the coaxial technique of the PCL systems, it was found that the particles size gets larger under the application of the higher ratio of inner-to-outer liquid flow rates. The primary particles formed out of an electrospraying nozzle showed narrow particle size distribution, but once they arrived to the collecting part, aggregation behavior was observed obviously. Efficient nano-encapsulation of albumin with PCL, PEG, and chitosan was conveniently achieved using electrospraying at above 12 kV.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.9 no.1
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• pp.9-16
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• 2023

Liposomes as drug delivery system have proved useful carrier for various disease, including cancer. In addition, perfluorocarbon cored microbubbles are utilized in conjunction with high-intensity focused-ultrasound (HIFU) to enable simultaneous diagnosis and treatment. However, microbubbles generally exhibit lower drug loading efficiency, so the need for the development of a novel liposome-based drug delivery material that can efficiently load and deliver drugs to targeted areas via HIFU. This study aims to develop a liposome-based drug delivery material by introducing a substance that can burst liposomes using ultrasound energy and confirm the ability to target tumors using PET imaging. Liposomes (Lipo-DOX, Lipo-DOX-Au, Lipo-DOX-Au-RGD) were synthesized with gold nanoparticles using an avidin-biotin bond, and doxorubicin was mounted inside by pH gradient method. The size distribution was measured by DLS, and encapsulation efficiency of doxorubicin was analyzed by UV-vis spectrometer. The target specificity and cytotoxicity of liposomes were assessed in vitro by glioblastoma U87mg cells to HIFU treatment and analyzed using CCK-8 assay, and fluorescence microscopy at 6-hour intervals for up to 24 hours. For the in vivo study, U87mg model mouse were injected intravenously with 1.48 MBq of ⁶⁴Cu-labeled Lipo-DOX-Au and Lipo-DOX-Au-RGD, and PET images were taken at 0, 2, 4, 8, and 24 hours. As a result, the size of liposomes was 108.3 ± 5.0 nm at Lipo-DOX-Au and 94.1 ± 12.2 nm at Lipo-DOX-Au-RGD, and it was observed that doxorubicin was mounted inside the liposome up to 52%. After 6 hours of HIFU treatment, the viability of U87mg cells treated with Lipo-DOX-Au decreased by around 20% compared to Lipo-DOX, and Lipo-DOX-Au-RGD had a higher uptake rate than Lipo-DOX. In vivo study using PET images, it was confirmed that ⁶⁴Cu-Lipo-DOX-Au-RGD was taken up into the tumor immediately after injection and maintained for up to 4 hours. In this study, drugs released from liposomes-gold nanoparticles via ultrasound and RGD targeting were confirmed by non-invasive imaging. In cell-level experiments, HIFU treatment of gold nanoparticle-coupled liposomes significantly decreased tumor survival, while RGD-liposomes exhibited high tumor targeting and rapid release in vivo imaging. It is expected that the combination of these models with ultrasound is served as an effective drug delivery material with therapeutic outcomes.

• Parasites, Hosts and Diseases
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• v.61 no.1
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• pp.33-41
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• 2023

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED₅₀ values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

• Clinical and Experimental Pediatrics
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• v.60 no.2
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• pp.50-54
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• 2017

Purpose: The aims of this study were to evaluate the safety and pharmacokinetics of levetiracetam (LEV) in neonates with seizures and to establish a population pharmacokinetics (PPK) model by using the software NONMEM. Methods: A retrospective analysis of 18 neonatal patients with seizures, who were treated with LEV, including 151 serum samples, was performed. The mean loading dose was 20 mg/kg, followed by a mean maintenance dose of 29 mg/kg/day. Results: Seventeen neonates (94%) had seizure cessation within 1 week and 16 (84%) remained seizure-free at 30 days under the LEV therapy. The mean serum concentration of LEV was $8.7{\mu}g/mL$. Eight samples (5%) were found above the therapeutic range. No serious adverse effects were detected. In the PPK analysis for Korean neonates, the half-life was 9.6 hours; clearance, 0.357 L/hr; and volume of distribution, 4.947 L, showing differences from those in adults. Conclusion: LEV is a safe and effective option for the treatment of neonatal seizures with careful therapeutic drug monitoring.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6463-6468
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• 2012

Purpose: To evaluated the effect of the gambogic acid (GA), one of the effective components of Garcinia, in combination with a new multi-targeted oral medication, sunitinib (SU) on renal cancer cell proliferation in vitro and on tumor growth in vivo. Methods: After treatment with GA or SU, either alone or in combination, MTT and FACS analysis were used to examine cell viability and cycle distribution of the renal carcinoma cell lines 786-0 and Caki-1. Western blotting was employed to examine the expression of proteins related to the cell cycle and vascular formation. Furthermore, a xenograft model was applied to study the antitumor efficacy of SU or GA alone or in combination, with immunohistochemistry to detect expression of proteins related to xenograft growth and angiogenesis. Western blotting was used to examine NF-${\kappa}B$ signaling pathway elements in xenografts. Results: Treatment of 786-0 and Caki-1 cells with GA or SU resulted in decreased tumor cell proliferation, especially with joint use. Cells accumulated more strongly in the sub-G1 phase after joint treatment with GA and SU than treatment of GA and SU alone. Western blotting arrays showed 1 protein significantly upregulated, 2 proteins downregulated, and 2 proteins unchanged. Moreover, combined use of GA and SU inhibited the growth and angiogenesis of xenografts generated from Caki-1 significantly. Immunohistochemistry arrays showed downregulation of the expression of proteins promoting xenograft growth and angiogenesis, and Western blotting showed inhibition of the NF-${\kappa}B$ signaling pathway after treatment by GA alone and in combination with SU in xenografts. Conclusions: Our results show that the joint use of GA and SU can provide greater antitumor efficacy compared to either drug alone and thus may offer a new treatment strategy for renal cell carcinoma.