• Title/Summary/Keyword: cell permeability

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In vitro Transport of Fexofenadine.HCl in Deformable Liposomes Across the Human Nasal Epithelial Cell Monolayers

  • Lin, Hong-Xia;Lee, Chi-Ho;Shim, Chang-Koo;Chung, Suk-Jae;Kim, Dae-Duk
    • Journal of Pharmaceutical Investigation
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    • v.34 no.6
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    • pp.483-489
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    • 2004
  • Fexofenadine HCl is non-sedating histamine H1 receptor antagonist that can be used for the treatment of seasonal allergic rhinitis. The objective of this study was to investigate whether the carriers of deformable liposomes can enhance the transepithelial permeability of fexofenadine HCl across the in vitro ALI human nasal monolayer model. Characterization of this model was achieved by bioelectric measurements and morphological studies. The passage 2 and 3 of cell monolayers exhibited the TEER value of $2852\;{\pm}\;482\;ohm\;{\times}\;cm^2$ on 11 days of seeding and maintained high TEER value for 5 days. The deformable liposome of fexofenadine HCl was prepared with phosphatidylcholine (PC) and cholic acid using extruder method. The mean particle size was about 200 nm and the maximum entrapment efficiency of 33.0% was obtained in the formulation of 1% PC and $100\;{\mu}g/ml$ fexofenadine HCl. The toxicity of the deformable liposome to human nasal monolayers was evaluated by MTT assay and TEER value change. MTT assay showed that it has no toxic effect on the nasal epithelial cells in 2-hour incubation when the PC concentration was below 1%. However, deformable liposome could not enhance the transepithelial permeability $(P_{app})$ and cellular uptake of fexofenadine HCl. In conclusion, the in vitro model could be used in nasal drug transport studies and evaluation of transepithelial permeability of formulations.

High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity

  • Park, Mi-Young;Kim, Min Young;Seo, Young Rok;Kim, Jong-Sang;Sung, Mi-Kyung
    • Journal of Cancer Prevention
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    • v.21 no.2
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    • pp.95-103
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    • 2016
  • Background: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in $Apc^{Min/+}$ mice. Methods: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. Results: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2'-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). Conclusions: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

Extrapolation of Hepatic Concentrations of Industrial Chemicals Using Pharmacokinetic Models to Predict Hepatotoxicity

  • Yamazaki, Hiroshi;Kamiya, Yusuke
    • Toxicological Research
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    • v.35 no.4
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    • pp.295-301
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    • 2019
  • In this review, we describe the absorption rates (Caco-2 cell permeability) and hepatic/plasma pharmacokinetics of 53 diverse chemicals estimated by modeling virtual oral administration in rats. To ensure that a broad range of chemical structures is present among the selected substances, the properties described by 196 chemical descriptors in a chemoinformatics tool were calculated for 50,000 randomly selected molecules in the original chemical space. To allow visualization, the resulting chemical space was projected onto a two-dimensional plane using generative topographic mapping. The calculated absorbance rates of the chemicals based on cell permeability studies were found to be inversely correlated to the no-observed-effect levels for hepatoxicity after oral administration, as obtained from the Hazard Evaluation Support System Integrated Platform in Japan (r = -0.88, p < 0.01, n = 27). The maximum plasma concentrations and the areas under the concentration-time curves (AUC) of a varied selection of chemicals were estimated using two different methods: simple one-compartment models (i.e., high-throughput toxicokinetic models) and simplified physiologically based pharmacokinetic (PBPK) modeling consisting of chemical receptor (gut), metabolizing (liver), and central (main) compartments. The results obtained from the two methods were consistent. Although the maximum concentrations and AUC values of the 53 chemicals roughly correlated in the liver and plasma, inconsistencies were apparent between empirically measured concentrations and the PBPK-modeled levels. The lowest-observed-effect levels and the virtual hepatic AUC values obtained using PBPK models were inversely correlated (r = -0.78, p < 0.05, n = 7). The present simplified PBPK models could estimate the relationships between hepatic/plasma concentrations and oral doses of general chemicals using both forward and reverse dosimetry. These methods are therefore valuable for estimating hepatotoxicity.

A Study on Inset Fed Microstrip Antenna Loaded with Complementary Single Loop Resonator (CSLR을 갖는 인셋 급전 마이크로스트립 안테나에 관한 연구)

  • Hong, Jae-Pyo;Kim, Byung-Mun
    • The Journal of the Korea institute of electronic communication sciences
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    • v.9 no.8
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    • pp.921-926
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    • 2014
  • In this paper, the characteristics of inset fed microstrip antenna loaded with CSLR(complementary single loop resonator) are studied. Effective permeability parameters of the SLR unit cell is retrieved from simulated scattering parameters, and structure parameters of the SLR unit cell are selected so that effective permeability is negative value at the operating frequency. The optimized inset fed microstrip antenna loaded with SLR for a $3{\times}3$ array in the ground plane of a conventional patch antenna is designed and simulation results of return loss and radiation pattern are shown. At resonant frequency 2.82 GHz, the overall dimension of the proposed antenna is reduced by approximately 56.8% compared to the conventional inset fed antenna. Simulation results are obtained by 3D FEM solver(Ansoft's HFSS).

Inhibitory Effect of Saururus chinensis (Lour.) Baill Extracts on Allergy in Mouse Models (Mouse 모델 알레르기 반응에서 삼백초(三白草)가 미치는 영향)

  • Suk, Min-Hee;Kang, Kyung-Hwa;Choi, Yung-Hyun;Choi, Byung-Tae;Lee, Yong-Tae
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.1
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    • pp.146-151
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    • 2005
  • We investigated the effect of Saururus chinensis (Lour.) Baill (SCB) on allergy in mice. We conformed compound 48/80-induced mesenteric mast cell degranulation, active systemic anaphylatic shock and histamine release. Also observed acetic acid-induced vascular permeability and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. SCB inhibited mesenteric mast cell degranulation and active systemic anaphylatic shock induced by compound 48/80 dose-dependently. When SCB was pretreated by intra-peritoneal injection, the plasma histamine levels were reduced. SCB also significantly inhibited acetic acid-induced vascular permeability and anti-DNP IgE-mediated passive cutaneous anaphylaxis. In addition, SCB reduced IL-10 mRNA expression of the lung on ovalbumin-induced allergy. These results indicate that SCB inhibits allergy.

Design of Dual-band Metamaterial Absorber using Two Pairs of ELC Resonators (두 쌍의 ELC 공진기를 이용한 이중 대역 메타 흡수체의 설계)

  • Lee, Hyung-Sup;Lee, Hong-Min
    • The Journal of Korea Institute of Information, Electronics, and Communication Technology
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    • v.5 no.1
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    • pp.26-32
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    • 2012
  • This paper presents a metamaterial absorber unit sell structure with four-element electric-LC resonators (ELC). In order to enhance the operating bandwidth of the proposed absorber unit cell two pairs of ELC resonators with a different size are used. The proposed unit cell shows negative permittivity and permeability when the electric field is parallel to the capacitive gap and the magnetic field is normal to the plane of ELC resonator. The simulated results show peak absorbance over 90% at two frequencies of 8.53 and 9.08 GHz, respectively.

Degradation of Membrane for PEM Fuel Cell with Hydrogen Peroxide (과산화수소에 의한 고분자전해질 연료전지 막의 열화)

  • Kim, Tae-Hee;Lee, Jung-Hun;Park, Kwon-Pil
    • 한국신재생에너지학회:학술대회논문집
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    • 2006.11a
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    • pp.438-442
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    • 2006
  • The degradation of Nafion membrane by hydrogen peroxide was investigated in polymer electrolyte membrane fuel cell (PEMFC). Degradation tests were carried out in a solution of $10{\sim}30%$ hydrogen peroxide containing 4ppm $Fe^{2+}$ ion which is well known as Fenton's reagent at $80^{\circ}C$ for 48hr. Characterization of degraded membranes were examined through the IR, Water-uptake, Ion exchange capacity, mechanical strength and $H_2$ permeability. After degradation, C-F, S-O and C-O chemical bonds of membrane were broken by radical formed by $H_2O_2$ decomposition. Breaking of C-F bond which is the membrane backbone reduced the mechanical strength of Nafion membrane and hence induced pinholes, resulting in increase of $H_2$ crossover through the membrane. Also the decomposition of C-O and S-O, side chain and terminal bond of membrane, decreased the ion exchange capacity of the membrane.

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Improvement of Dissolution Rate of Poorly Water Soluble Drug Using Self-microemulsifying Drug Delivery System (SMEDDS를 이용한 난용성 약물의 용출율 향상)

  • Kim, Kye-Hyun;Rhee, Yun-Seok;Bae, Joon-Ho;Chi, Sang-Cheol;Park, Eun-Seok
    • Journal of Pharmaceutical Investigation
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    • v.29 no.1
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    • pp.37-45
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    • 1999
  • ABSTRACT-A self-microemulsifying drug delivery system (SMEDDS) was developed to enhance the solubility and dissolution rate of poorly water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The system was optimized by evaluating the solubility of DDB and the microemulsion existence range after the preparation of microemulsions with varying compositions of triacetin and surfactant-cosurfactant mixtures (Labrasol as surfactant (S) and the combination of Transcutol, Cremophor RH 40 and Plurol oleique as cosurfactant (CoS)). SMEDDS in this study markedly improved the solubility of DDB in water up to 10 mg/ml and the size of the o/w microemulsion droplets measured by dynamic light scattering showed a narrow monodisperse size distribution with an average diameter less than 50 nm. The microemulsion existing range is increased proportional to the ratio of S/CoS, however, it decreased remarkably as the oil content was more than 20%. In vitro dissolution study of SMEDDS showed a significantly increased dissolution rate of DDB in water (> 12 fold over DDB powder), and SMEDDS also had significantly greater permeability of DDB in Caco-2 cell compared to powders.

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Analysis of Shielding Effectiveness and Estimation of Shielding Factor in Conductive and Magnetic Shields (도전성 및 자성 차폐체의 차폐효과 해석과 차폐인수 산정)

  • Kang, Dae-Ha
    • Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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    • v.27 no.10
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    • pp.30-40
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    • 2013
  • In this study the method based on flux linkage in cell was introduced in calculation of eddy currents by cell method. According to this method eddy current distribution and the loss can be evaluated and since the shielding effectiveness by flux cancelation of eddy current can be analyzed, this method is applicable to design of conductive shield. And also the formula of shielding factor were so deduced as to be applicable to finite-width infinite-length shielding sheets and infinite-length underground cable shield. These formula are adaptable to magnetic materials as well as conductive materials. As the results of calculation in model shields are follows. In case of finite-width infinite-length shielding sheet, shielding effectiveness increases with increasing of conductivity. In case of infinite-length underground cable shield, the effectiveness become higher with increasing of permeability. Especially the effectiveness is very high in materials with both high conductivity and permeability in underground cable shield.

Effect of Saururus chinensis (Lour.) Baill. Aquacupuncture on Anaphlylaxis in Mice (삼백초약침액(三白草藥鍼液)이 아나필락시스에 미치는 영향)

  • Choi, Kyu-Jung;Lee, So-Young;Kang, Kyung-Hwa;Lee, Yong-Tae;Song, Choon-Ho
    • Korean Journal of Acupuncture
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    • v.21 no.3
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    • pp.97-104
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    • 2004
  • Objective We investigated the effect of Saururus chinensis (Lour.) Baill. aquacupuncture (SCB) on anaphylaxis in mice. Methods : We conformed compound 48/80-induced mesenteric mast cell degranulation, active systemic anaphylatic shock and histamine release. Also observed acetic acid-induced vascular permeability and anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. Results : SCB inhibited mesenteric mast cell degranulation and active systemic anaphylatic shock induced by compound 48/80 dose-dependently. When SCB was pretreated by intra-peritoneal injection, the serum histamine levels were reduced. SCB also significantly inhibited acetic acid-induced vascular permeability. In addition, SCB showed a significant inhibitory effect on anti-dinitrophenyl (DNP) IgE-mediated passive cutaneous anaphylaxis. Conclusion : These results indicated that SCB inhibits anaphylatic reaction.

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