• Genomics & Informatics
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• v.19 no.4
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• pp.39.1-39.8
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• 2021

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)-positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) 'biological process' terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7 breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including 'cell cycle' (cdc2, rik1, pas1, and leo1), 'signaling' (sck2, oga1, and cki3), and 'vesicle-mediated transport' (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the 'signaling' GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

• CELLMED
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• v.4 no.3
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• pp.17.1-17.8
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• 2014

Herbal remedies are commonly used by patients worldwide. Because these herbal preparations share the same metabolic and transport proteins with prescribed medicines, the potential for a drug-herb interaction is substantial and is an issue of significant concern. This review paper summarizes drug-herb interactions involving inhibition or induction of cytochrome P450 enzymes, drug transporters as well as modulation of drug pharmacodynamics. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and implications of these studies are discussed in this review. The most commonly implicated drugs in the interaction include anticoagulants, antiplatelets, immunosuppressants, anti-neoplastics, protease inhibitors, and some antidepressants. Pharmacokinetic and/or pharmacodynamic interactions of five commonly used herbal remedies (danshen, garlic, Ginkgo biloba, ginseng, and St John's wort) with these drugs are presented, with focus of discussion being the potentials for interaction, their mechanisms and clinical implications. There is a necessity for adequate pharmacovigilance to be carried out in minimizing unanticipated but often preventable drug-herb interactions.

• Archives of Pharmacal Research
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• v.2 no.1
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• pp.65-70
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• 1979

Distribution and binding properties of sodium salicylate the human red blood cells were studied under various experimental conditions. The effect of tonicity and hemolysis on the steady state level of the drug within the human red blood cells were accounted for in this study. When the washed cells were suspended in normal saline solution, the drug was so rapidly permeated into red cells. Since the pH of the system forces nearly complete ionization of the drug, ionic diffusion through aqueous pores is thought to be the mode of salicylate transport. Human red cell binding capacity and association constant for salicylate were estimated. This work supports the view that the red cells act asan important reservior of salicylate.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.23-31
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• 2010

In our previous work on levodopa delivery at pH 2.5 using iontophoresis, we found that cathodal delivery showed higher permeation than anodal delivery and electroosmosis plays more dominant role than electrorepulsion. In this work, we studied the transdermal transport of levodopa at very low pH (pH=1.0) where all levodopa molecules are cations, and evaluated some factors which affect the transdermal transport. The transport study at pH 2.5 was also conducted for comparison. The contribution of electrorepulsion and electroosmosis on flux was also evaluated. Using stable aqueous solution, the effect of electrode polarity, current density, current type and drug concentration on transport through skin were studied and the results were compared. We also investigated the iontophoretic flux from hydroxypropyl cellulose (HPC) hydrogel containing levodopa. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell. Full thickness hairless mouse skin were used. Current densities applied were 0.2, 0.4 or $0.6\;mA/cm^2$. Contrary to the pH 2.5 result, anodal delivery showed higher flux, indicating that electrorepulsion is the dominant force for the transport, overcoming the electroosmotic flow which is acting against the direction of electrorepulsion. Cumulative amount of levodopa transported was increased as the current density or drug concentration was increased. When amount of current dose was constant, continuous current was more beneficial than pulsed current in promoting levodopa permeation. Similar transport results were obtained when hydrogel was used as the donor phase. These results indicate that iontophoretic delivery of zwitterion such as levodopa is much complicated than that can be expected from small ionic molecules. The results also indicate that, only at very low pH like pH 1.0, electrorepulsion can be the dominant force over the electroosmosis in the levodopa transport.

• Journal of Pharmaceutical Investigation
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• v.32 no.1
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• pp.21-26
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• 2002

The primary culture of human nasal epithelial cell monolayer was performed on a Transwell. The effect of various factors on the tight junction formation was observed in order to develop an in vitro experimental system for nasal transport studies. Human nasal epithelial cells, collected from human normal inferior turbinates, were plated onto diverse inserts. After 4 days, media of the apical surface was removed for air-liquid interface (ALI) culture. Morphological characteristics was observed by transmission electron microscopy (TEM). A polyester membrane of $0.4\;{\mu}m$ pore size was determined as the most effective insert based on the change in the transepithelial electric resistance (TEER) value as well as the $^{14}C-mannitol$ transport study. The ALI method was effective in developing the tight junction as observed in the further increase in the TEER value and reduction in the permeability coefficient $(P_{app})$ of $^{14}C-mannitol$ transport. Results of the transport study of a model drug, budesonide, showed that the primary culture system developed in this study could be further developed and applied for in vitro nasal transport studies.

• Korean Journal of Biological Psychiatry
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• v.6 no.1
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• pp.49-66
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• 1999

Polypharmacotherapy, both psychotropic and nonpsychotropic, is widespread in various situations including psychiatric hospitals and general hospitals. As the clinical practice of using more than one drug at a time increase, the clinician is faced with ever-increasing number of potential drug interactions. Although many interactions have little clinical significances, some may interfere with treatment or even be life-threatening. The objective of this review is evaluation for drug-drug interactions often encountered in psychiatric consultation. Drug interactions can be grouped into two principal subdivisions : pharmacokinetic and pharmacodynamic. These subgroups serve to focus attention on possible sites of interaction as a drug moves from the site of administration and absorption to its site of action. Pharmacokinetic processes are those that include transport to and from the receptor site and consist of absorption, distribution on body tissue, plasma protein binding, metabolism, and excretion. Pharmacodynamic interactions occur at biologically active sites. In psychiatric consultation, these two subdivisions of drug interactions between psychotropic drugs and other drugs are likely to happen. We gathered informations of the drugs used in physically ill patients who are consulted to psychiatric department in Korea University Hospital. And we reviewed the related literatures about the drug-drug interactions between psychotropic drugs and other drugs.

• Advances in nano research
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• v.14 no.2
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• pp.165-177
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• 2023

Nanomotors are gaining popularity as novel drug delivery methods since they can move rapidly, penetrate deeply into tissues, and be regulated. The ability of manufactured nanomotors to swiftly transport therapeutic payloads to their intended location constitutes a revolutionary nanomedicine strategy. The nanomotors for the drug delivery purpose are released in the blood flow under the different physical conditions, so the stability investigation of these devices is essential before the production, especially in the sport and physical exercise conditions that the blood flow enhances. As a result, using dynamic analysis, this article investigates the stability of the nanomotor released in the blood flow when sport and physical activity circumstances increase blood flow. The considered nanodevice is made of a central motor, and nanotubes are used for the nanomotor blade, which is the drug capsule. Finally, the stability examination of nanomotor as the drug delivery equipment is discussed in detail, and the proposed results can present beneficial results in designing and producing small-scale intelligent devices.

• 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.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.498-505
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• 2021

Amyotrophic lateral sclerosis (ALS) is a lethal neurological disorder characterized by the deterioration of motor neurons. The aim of this study was to investigate alteration of cationic amino acid transporter (CAT-1) activity in the transport of lysine and the pretreatment effect of lysine on pro-inflammatory states in an amyotrophic lateral sclerosis cell line. The mRNA expression of cationic amino acid transporter 1 was lower in NSC-34/hSOD1^G93A (MT) than the control cell line (WT), lysine transport is mediated by CAT-1 in NSC-34 cell lines. The uptake of [³H]L-lysine was Na⁺-independent, voltage-sensitive, and strongly inhibited by inhibitors and substrates of cationic amino acid transporter 1 (system y⁺). The transport process involved two saturable processes in both cell lines. In the MT cell line, at a high-affinity site, the affinity was 9.4-fold higher and capacity 24-fold lower than that in the WT; at a low-affinity site, the capacity was 2.3-fold lower than that in the WT cell line. Donepezil and verapamil competitively inhibited [³H]L-lysine uptake in the NSC-34 cell lines. Pretreatment with pro-inflammatory cytokines decreased the uptake of [³H]L-lysine and mRNA expression levels in both cell lines; however, the addition of L-lysine restored the transport activity in the MT cell lines. L-Lysine exhibited neuroprotective effects against pro-inflammatory states in the ALS disease model cell lines. In conclusion, studying the alteration in the expression of transporters and characteristics of lysine transport in ALS can lead to the development of new therapies for neurodegenerative diseases.

• Elastomers and Composites
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• v.54 no.2
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• pp.149-155
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• 2019

Controlled mass transport in response to stimuli is essential for drug carriers. The complexity of the signaling system under physiological conditions has led researchers to develop precise nanocontainers that respond to stimuli in the physiological environment. Owing to several reasons, soft nanocontainers such as liposomes and micelles have been investigated for use as drug delivery systems. However, such carriers often suffer from the undesired leakage of drug molecules. In contrast, inorganic nanocontainers are robust, and their surfaces can be easily functionalized. For example, mesoporous silica nanoparticles equipped with gatekeeper molecules are increasingly being used for the controlled release of drug molecules in response to the desired stimuli. Since the development of the first hybrid nanocontainer comprising molecular machines, multiple versions of such gatekeeper systems featuring significantly improved stability and precise response to stimuli have been reported. In this study, various methods for incorporating photoresponsive nanocontainers with porous channels are developed.