• Journal of Pharmaceutical Investigation
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• 제41권1호
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• pp.9-17
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• 2011

The objective of this work is to study transdermal delivery of calcitonin using iontophoresis and to evaluate various factors which affect the transdermal transport. We have studied the effect of polarity, current density, drug concentration, penetration enhancers (isopropyl myristate [IPM] and ethanol) and laser treatment on transdermal flux and the results were compared. We also investigated the iontophoretic flux from microemulsions containing calcitonin together with oleic acid (OA) or IPM. In vitro flux study was performed at $33^{\circ}C$, using side-by-side diffusion cell and full thickness hairless mouse skin. Anodal delivery at pH 3.0 was much larger than cathodal and passive delivery, due to the positive charge of calcitonin. Cumulative amount delivered (CUM) by cathodal or passive delivery was close to zero for 10 hours. The pretreatment of skin by neat IPM markedly increased the CUM anodically. CUM increased as the current density, drug concentration or the duration of IPM treatment increased. Microemulsion containing IPM or oleic acid was prepared and the phase diagram was constructed. CUM also increased when IPM was incorporated into a microemulsion. OA microemulsion showed similar enhancing effect to IPM microemulsion. The delivery of calcitonin from 70% (v/v) ethanol aqueous solution showed a large increase in flux. Laser treatment of skin before flux experiment exhibited about 2 fold increase in total calcitonin amount transported for 12 hours, when compared to that delivered by IPM microemulsion. Based on these results, we have evaluated the possibility of delivering enough amount of calcitonin to reach the therapeutic level. The data suggest that it is highly possible to deliver clinically effective amount of calcitonin using iontophoresis patch with small area (<10 $cm^2$).

• Biomolecules & Therapeutics
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• 제10권1호
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• pp.37-42
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• 2002

Brain drug targeting through the blood-brain barrier (BBB) in vivo is possible with peptidornirnetic monoclonal antibodies that undergo receptor-mediated transcytosis through the BBB. Monoclonal antibody to the rat transferrin receptor, such as the OX26 was studied in rats as a transport vector through BBB on the transferrin receptor. But, OX26 is not an effective brain delivery vector in mouse. In the present studies, rat monoclonal antibody, 8D3 to the mouse transferrin receptor were evaluated for brain drug targeting vector intransgenic mouse model. Pharrnacokinetic parameters in plasma and organ uptakes were determined at varioustimes after i.v. bolus injection of [$^{}125}I$] 8D3 in Balb/c mice. Brain uptake of [$^{}125}I$] 8D3 was also studied with an internal carotid artery perfusioncapillary depletion method. After i.v. injection of [$^{}125}I$] 8D3, plasma concentrations declined biexponentially with elimination half lift of approximately 2.2 hours. Brain uptake of [$^{}125}I$] 8D3 was $0.50{\pm}0.09$ persent of injected dose per g brain after 2 hours i.v. injection. After perfusion 5 min the apparent volume of distibution of [$^{}125}I$] 8D3 in brain was $22.3 {\mu}l/g,$ which was 4.8 fold higher than the intravascular volume. These studies indicate rat monoclonal antibody to the mouse transferrin receptor, 8D3 may be used for brain drug targeting vector in mice.

• Steel and Composite Structures
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• 제49권5호
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• pp.487-502
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• 2023

In the realm of nanotechnology, the nonlocal strain gradient theory takes center stage as it scrutinizes the behavior of spinning cantilever nanobeams and nanotubes, pivotal components supporting various mechanical movements in sport structures. The dynamics of these structures have sparked debates within the scientific community, with some contending that nonlocal cantilever models fail to predict dynamic softening, while others propose that they can indeed exhibit stiffness softening characteristics. To address these disparities, this paper investigates the dynamic response of a nonlocal cantilever cylindrical beam under the influence of external discontinuous dynamic loads. The study employs four distinct models: the Euler-Bernoulli beam model, Timoshenko beam model, higher-order beam model, and a novel higher-order tube model. These models account for the effects of functionally graded materials (FGMs) in the radial tube direction, giving rise to nanotubes with varying properties. The Hamilton principle is employed to formulate the governing differential equations and precise boundary conditions. These equations are subsequently solved using the generalized differential quadrature element technique (GDQEM). This research not only advances our understanding of the dynamic behavior of nanotubes but also reveals the intriguing phenomena of both hardening and softening in the nonlocal parameter within cantilever nanostructures. Moreover, the findings hold promise for practical applications, including drug delivery, where the controlled vibrations of nanotubes can enhance the precision and efficiency of medication transport within the human body. By exploring the multifaceted characteristics of nanotubes, this study not only contributes to the design and manufacturing of rotating nanostructures but also offers insights into their potential role in revolutionizing drug delivery systems.

• The Korean Journal of Physiology
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• 제21권2호
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• pp.157-167
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• 1987

Benzyl alcohol is known to have dual effect on the red blood cell shape change. At low concentration up to 50 mM benzyl alcohol transformed the shape from discocyte to stomatocyte by preferent binding to the inner hemileaflet, however, at higher concentratransformed the shape from discocyte to stomatocyte by preferential binding to the inner monolayer, however, at higher concentration above 50 mM benzyl alcohol transformed to echinocyte by affecting both monolayers. These results suggest that the effect of benzyl alcohol on the red blood cell shape and $Ca^{++}$ transport across cardiac cell membranes to assess the effects of the drug on the structures and functions of the biological cell membranes. The results are as follows: 1) Benzyl alcohol up to 40 mM caused progressive stomatocytic shap change of the red blood cell but above 50 mM benzyl alcohol caused echinocytic shape change. 2) Benzyl alcohol up to 40 mM inhibited both osmotic hemolysis and osmotic volume change of the red blood cell in hypotonic and hypertonic NaCl solutions, respectively. 3) Benzyl alcohol inhibited both Bowditch Staircase and Wood-worth Staircase phenomena at rat left auricle. 4) Benzyl alcohol at concentration of 5 mM increased $Ca^{++}-ATPase$ activity of red blood cell ghosts slightly but above S mM benzyl alcohol inhibited the $Ca^{++}-ATPase$ activity. 5) Benzyl alcohol at concentrations of 5 mM and 10 mM increased $Ca^{++}-ATPase$ activity slightly at rat gastrocnemius muscle S.R. but above 10 mM benzyl alcohol inhibited the $Ca^{++}-ATPase$ activity. Above results indicate that benzyl alcohol inhibit water permeability and $Ca^{++}$ transport across cell membranes in part via effects on the fluidity and transition temperatures of the bulk lipid by preferential intercalation into cytoplasmic monolayer and in part via other effect on the conformational change of active sites of the $Ca^{++}-ATPase$ molecule extended in cytoplasmic face.

• The Korean Journal of Physiology
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• 제13권1_2호
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• pp.13-22
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• 1979

Studies have been conducted using isolated surviving skin of Rana temporalia in an attempt to evaluate the effect of N-ethylmaleimide (NEM) on the epithelial $Na^+$ transport. Active transport of $Na^+$ across the skin was estimated by measuring short circuit current (SCC). NEM administered to the outside surface of the skin in concentration of $0.5{\times}10^{-4}-2.5{\times}10^{-4}M$ induced $20{\sim}40%$ increase during the first 30 mintues, followed by a gradual reduction in SCC. With NEM above $4{\times}10^{-4}M$, SCC was inhibited from the beginning. Qualitatively similar results were obtained when NEM was added to the inside bathing medium. However, the concentration of NEM for a similar effect was much higher with the drug in the inside bathing medium than in the outside bathing medium. The oxygen consumption of the skin was inhibited by NEM of above $10^{-4}M$, the effect being of approximately the same magnitude as that on SCC. The activity of $Na^+-K^+$ ATPase of the skin was not inhibited by NEM below $10^{-3}M$, but it was dramatically reduced with $1.2{\times}M$ NEM. The effects of NEM $(10^{-4}M)$ on the SCC and oxygen consumption could be eliminated by adding cysteine $(10^{-4}-10^{-3}M)$ in the medium, indicating that the SH group is involved in the action of NEM in the frog skin. On the basis of these results, the mode of action of NEM on the $Na^+$ transport across the frog skin was discussed.

• 대한한방내과학회지
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• 제11권2호
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• pp.148-169
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• 1990

The Present experiment was designed to investigate the effects of Soo Jeom San on the function of heart and digestive organs. And thus it was analyzed the total acidity, recovery effect, and the other various enzyme activities such as ATPase, Creatine kinase, Aspartate transaminase, and Lactate dehydrogenase. The results were obtained as follows : 1. The Total acidity decreased after Soo JeomSan administration for 6 days, however the total acidity inoreased after the drug administration for 9 days, these phenomena demonstrate that Soo Jeom San acts as a dual factor. The mechanism of decreasing the total acidity was considered to the inhibition of ATPase activity used for HCI active transport from parietal cells. 2. Soo Jeom San recovered the islets of Langerhans which was disrupted by streptozotocin. The recovery mechanism was suggested that Soo Jeom San stimulates the ${\beta}-cell$ proliferation. 3. Soo Jeom San inhibited the enzyme activities such as Creatine kinase and Aspartate transaminase, however the drug activated Lactate dehydrogenase. According to the obtained results, Soo Jeom San may be used for curing gastric ulcer and myocardiac infarction.

• 한국응용과학기술학회지
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• 제24권4호
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• pp.410-415
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• 2007

Functional cosmetics are intensively investigated for the effectiveness of skin whitening, anti-aging and slimming. For enhancing the effectiveness, active ingredients should be delivered into the cell in the dermis. The amounts of penetration of caffeine and $Arbutin^{(R)}$ were tested, in vitro, using Franz diffusion cell. Oil-in-water emulsions were used for the vehicles of the transport. For the measuring the amounts of active ingredients delivered into the dermal skin, tape stripping was done after finishing the penetration experiments. The amounts of delivered caffeine were $8.45{\pm}$ 1.26ug/ml before tape stripping and $3.45{\pm}$ 1.80ug/ml after tape stripping, however, the amounts of delivered $Arbutin^{(R)}$ was quite small to detect. From now on, proper vehicles are considered for enhancing the delivery of $Arbutin^{(R)}$ Hairless mouse skin was compared with pig skin as a transdermal delivery membrane. The aspects of delivery were similar, but the amount of delivered ingredients using pig skin was larger than that of using hairless mouse skin. Therefore, the pig skin would be considered as a membrane for drug delivery experiments.

• Journal of Pharmaceutical Investigation
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• 제13권4호
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• pp.153-172
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• 1983

The use of carrier systems for the delivery of drugs to areas in the body in need of pharmacological intervention is now the subject of intense research in many laboratories. Because of its obvious advantages (e.g. protection of drugs from hostile environments, facilitated target penetration and avoidance of side effects), drug delivery is expected to ease the pressure and expense of new drug development by making better use of drugs in existence. Generally, carrier-mediated delivery has been envisaged either as direct transport of drugs to a biological target by a carrier that will associate with it selectively, or as release of drugs from a carrier circulating in the blood or immobilized in tissues, at rates compatible with optimal action. One system that has attracted considerable attention is the use of liposomes as carriers of pharmacologically active agents. 154 references were reviewed with special emphasis on the targeting of drugs by use of liposomes in this respect. Recent advances in the other carrier systems and in methods for the preparation of liposomes were also reviewed briefly.

• Biotechnology and Bioprocess Engineering:BBE
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• 제8권5호
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• pp.279-285
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• 2003

Lidocaine and galactose loading tests were performed on a bioartificial liver (BAL), an extracorporeal medical device incorporating living hepatocytes in a cartridge without a transport barrier across the membranes. The concentration changes were analyzed using pharmacokinetic equations to evaluate the efficacy and limitation of the proposed method. Lidocaine and galactose were found to be suitable drugs for a quantitative evaluation of the BAL functions, as they did not interact with the plasma proteins or blood vessels, making their concentrations easy to determine. The drug concentration changes after drug loading were easily analyzed using pharmacokinetic equations, and the BAL functions quantitatively expressed by pharmacokinetic parameters, such as the clearance (CL) and galactose elimination capacity (GEC). In addition, these two drugs have already been used in clinical tests to evaluate human liver functions over long periods, and lidocaine CL values and GEC values reported for a normal human liver. Thus, a comparison of the CL and GEC values for the BAL and a natural liver revealed what proportion of normal liver functions could be replaced by the BAL.

• 약학회지
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• 제46권2호
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• pp.124-128
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• 2002

The nitrone-based free radical trapping reagent, $\alpha$-phenyl-n-tert-butyl nitrone (PBN) has been proposed as therapeutic agent for stroke. We used this for model drug of development of new drug for neuroprotection. The purpose of this study was to evaluate the blood-brain barrier (BBB) permeability of PBN in Sprague-Dawly (SD) rats. The BBB transport of PBN was investigated in SD rats using internal carotid artery perfusion (ICAP) method at a rate of 4 mι/min for 15 second. We also obtained pharmacokinetic parameters of PBN using single intravenous injection technique. When we estimated BBB permeability of PBN with ICAP method, the brain volume of distribution of PBN was 60.0 $\pm$ 12.0 $\mu\textrm{g}$/ι. The brain uptake of PBN after IV injection at 120 min was 0.15 $\pm$ 0.01%ID/g. The PBN was transported to the brain through the BBB well in rats, because PBN is small molecule (MW 177) and lipid-soluble (log P 1.23) compound.