Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp

Yan Zhou,Xin’an Wu,Guo-Qiang Zhang,Zhi Rao,Yang Yang,Qian Zhou,Hongyan Qin,Yuhui Wei 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.7

Venlafaxine (VLX) could be pumped out of the brain by P-glycoprotein (P-gp). Moreover, the expression of P-gp distributed in blood–brain barrier could be significantly induced by VLX. Thus, P-gp could be considered as the nature barrier for delivering of VLX to the brain. The aim of this study was to investigate whether the efflux function and increased expression of P-gp could be reversed by utilizing solid lipid nanoparticles (SLN). VLX solid lipid nanoparticles (VLX - SLN) were prepared and evaluated. Pharmacokinetics and brain distribution of VLX in different formulations were conducted after oral or intravenous administration. P-gp efflux function to VLX was evaluated by the brain uptake amount of VLX, while P-gp expression was investigated by Western blotting. Results indicated that the entrapment, mean size and zata potential of VLX - SLN was 74.9 ± 3.0 %, 186.3 ± 69.26 nm and -22.8 ± 7.78 mv, respectively. After vein injection of VLX formulations, the brain uptake amount of VLX from VLX - SLN was significantly higher than that of VLX solution, VLX solution with empty SLN (VLX? empty SLN) and VLX solution with Verapamil (VLX ? Ver), respectively. Furthermore, the protein mass of P-gp in VLX - SLN treated group was the lowest among all the investigated groups. These results indicated that SLN could overcome P-gp and achieve brain target by intravenous administration.

Effects of Pluronic F68 and Labrasol on the Intestinal Absorption and Pharmacokinetics of Rifampicin in Rats

Li Ma,Xin'an Wu,Yuhui Wei,Yan Zhou,Xiaohua Ma 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.11

The aim of this study was to investigate the effects of Pluronic F68 and Labrasol on the intestinal absorption and pharmacokinetics of rifampicin. Intestinal permeability of rifampicin with or without excipients was evaluated by an in situ single-pass perfusion method. A highperformance liquid chromatographic method was applied to study the pharmacokinetics of rifampicin with or without excipients. Labrasol or Pluronic F68 (0.1% and 0.05%, v/v), co-perfused with rifampicin (60 μg/mL), significantly increased in situ permeability. Similarly, verapamil (a typical P-gp inhibitor) also increased in situ permeability, but to a lesser extent. In vivo, the oral administration of rifampicin with or without Pluronic F68, Labrasol or verapamil resulted in statistically significant effect on t1/2 (4.83 to 7.75, 6.42 and 7.46 h) and total body clearance (0.46 to 0.26, 0.28, 0.24 L/h/kg). In addition, Pluronic F68, Labrasol and verapamil produced minor changes in AUC_0-t, which improved 1.55-, 1.54-, and 1.73-fold in comparison to control group, respectively. These results showed that Labrasol and Pluronic F68 might inhibit the function of P-gp in the intestine, thereby increasing intestinal absorption and changing the pharmacokinetic parameters of rifampicin. Therefore, excipient selection is an important factor to consider in rational formulation design.

Gadolinium- and lead-containing functional terpolymers for low energy X-ray protection

Yu-Juan Zhang,Xin-Tao Guo,Chun-Hong Wang,Xiang An Lu,De-Feng Wu,Ming Zhang 한국원자력학회 2021 Nuclear Engineering and Technology Vol.53 No.12

By polymerization of gadolinium methacrylate (Gd (MAA)3), lead methacrylate (Pb(MAA)2) and methylmethacrylate (MMA), Gd and Pb were chemically bonded into polymers. The X-ray shielding performance was evaluated by Monte Carlo simulation method, and the results showed that the more metalfunctional organic monomer, the better the shielding performance of terpolymers. When the X-rayenergy is 65 keV, Gd (MAA)3-containing polymers have better shielding performance than Pb(MAA)2-containing polymers. Gd could compensate for the weak absorption region of Pb. Therefore, polymerscontaining both Gd and Pb enhanced shielding efficiency against X-ray in various low-energy ranges. Forobtaining terpolymers with uniform monomer compositions, the relationship between the monomercomposition of the terpolymers and the conversion level was optimized by calculating the reactivityratios. The value of reactivity ratios of r (Gd (MAA)3/Pb(MAA)2), r (Pb(MAA)2/Gd (MAA)3), r (Gd (MAA)3/MMA), r (MMA/Gd (MAA)3), r (Pb(MAA)2/MMA) and r (MMA/Pb(MAA)2) was 0.483, 0.004, 0.338, 2.508,0.255, 0.029. The terpolymers with uniform monomer composition could be obtained by controlling themonomer compositions or conversion levels. The results can provide new radiation protection materialsand contribute to the improvement in nuclear safety.

Ethosomes, Binary Ethosomes and Transfersomes of Terbinafine Hydrochloride: A Comparative Study

Jian-Ping Zhang,Xin-An Wu,Yu-Hui Wei,Yan Zhou,Yu-Qing Li 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.1

The aim of this study was to compare the skin permeation of ethosomes, binary ethosomes and transfersomes of Terbinafine Hydrochloride (TH) under non-occlusive conditions. These lipid vesicles were prepared and characterized for shape, size, zeta-potential and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption studies. The quantity of drug in the skin from ethosomes, binary ethosomes (the weight ratio of ethanol to propylene glycol 7:3, ethanol-PG = 7:3, w/w), and transfersomes was 1.26, 1.51 (p <0.05), 1.56 (p <0.01) times higher than that of TH from traditional liposomes (control). The skin deposition of the applied dose (DD%) of TH from ethosomes, binary ethosomes, and transfersomes was 3.34 (p < 0.05), 9.88 (p < 0.01), 2.52 times higher than that of TH from control. The results of CLSM experiments showed that penetration depth and fluorescence intensity of Rhodamine B from binary ethosomes was much greater than that from ethosomes and transfersomes. These results indicated the binary ethosomes (ethanol-PG = 7:3, w/w) most effectively permitted drug penetration through skin; transfersomes made drug easiest to accumulate in the skin. Ethosomes improved drug delivery with greater improvement in skin permeation than improvement in skin deposition.

Tissue distribution of sialic acid-linked influenza virus receptors in beagle dogs

Zhang-Yong Ning,Xin-Tao Wu,Yan-Fen Cheng,Wen-Bao Qi,Yu-Fu An,Heng Wang,Gui-Hong Zhang,Shou-Jun Li 대한수의학회 2012 Journal of Veterinary Science Vol.13 No.3

Reports of influenza A virus infections in dogs has received considerable attention from veterinarians, virologists, and epidemiologists. Interaction between influenza viral hemagglutinin and cell oligosaccharides containing sialic acid residues results in infection. Sialic acids have an α-2,3-linkage to the penultimate galactose in the avian influenza virus receptor and an α-2,6-linkage in the human receptor. To date,there are no detailed data on the tissue distribution or histological features of either type of sialic acid-linked influenza virus receptors in beagle dogs, which are common laboratory animals and pets. We conducted the current study to visualize the in situ tissue distribution of both sialic acid-linked influenza virus receptors in various organs of beagle dogs using Maackia amurensis lectin II and Sambucus nigra agglutinin. Both α-2,3- and α-2,6-sialic acid-linked receptors were detected in the endothelial cells of the respiratory tract and other organs. Endothelial cells of most gastrointestinal organs were negative for α-2,3-sialic acid-linked receptors in the dogs. Our results suggested that these canine organs may be affected by influenza virus infection. The findings from our study will also help evaluate the occurrence and development of influenza virus infections in dogs.

DEVELOPMENT OF CHINA LIGHT-DUTY VEHICLE TEST CYCLE

Yu Liu,Zhi Xin Wu,Hua Zhou,Han Zheng Nan Yu,Xiao Pan An,Jing Yuan Li,Meng Liang Li 한국자동차공학회 2020 International journal of automotive technology Vol.21 No.5

Driving cycles provide a basis for vehicle development and calibration and also serves as the foundation for energy consumption and emissions certification of vehicles. This paper presents the China Light-Duty Vehicle Test Cycle (CLTC) developed by the China Automotive Technology & Research Center (CATARC). First, the important steps and technical routes toward the CLTC development process are summarized. Second, the specific CLTC development process is presented in detail, including the data acquisition and data analysis procedures, weighting factor development and driving cycle construction. Then, the main driving characteristics of the New European Driving Cycle (NEDC), the Worldwide Harmonized Light-Duty Vehicles Test Cycle (WLTC), the Federal Test Procedure (FTP-75), the CLTC and the actual collected data are compared. The CLTC has low average speed, a high idle speed ratio and more frequent acceleration and deceleration characteristics. Finally, 70 vehicles are t ested based on the NEDC, WLTC, and CLTC according to their legislative procedures in the vehicle emission laboratories of the CATARC and the manufacturers. The results show that the CLTC’s fuel consumption is much higher than that of the NEDC and WLTC, and CLTC can effectively reflect the actual fuel consumption of users.

Luciferase Assay to Screen Tumour-specific Promoters in Lung Cancer

Xu, Rong,Guo, Long-Jiang,Xin, Jun,Li, Wen-Mao,Gao, Yan,Zheng, You-Xian,Guo, You-Hong,Lin, Yang-Jun,Xie, Yong-Hua,Wu, Ya-Qing,Xu, Rui-An Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

Objective: Specific promoters could improve efficiency and ensure the safety of gene therapy. The aim of our study was to screen examples for lung cancer. Methods: The firefly luciferase gene was used as a reporter, and promoters based on serum markers of lung cancer were cloned. The activity and specificity of seven promoters, comprising CEACAM5 (carcinoembryonic antigen, CEA), GRP (Gastrin-Releasing Peptide), KRT19 (cytokeratin 19, KRT), SFTPB (surfactant protein B, SP-B), SERPINB3 (Squamous Cell Carcinoma Antigen, SCCA), SELP (Selectin P, Granule Membrane Protein 140kDa, Antigen CD62, GMP) and DKK1 (Dickkopf-1) promoters were compared in lung cancer cells to obtain cancer-specific examples with strong activity. Results: The CEACAM5, DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB promoters were cloned. Furthermore, we successfully constructed recombinant vector pGL-CEACAM5 (DKK1, GRP, SELP, KRT19, SERPINB3 and SFTPB) contained the target gene. After cells were transfectedwith recombinant plasmids, we found that the order of promoter activity from high to low was SERPINB3, DKK1, SFTPB, KRT19, CEACAM5, SELP and GRP and the order for promoters regarding specificity and high potential were SERPINB3, DKK1, SELP, SFTPB, CEACAM5, KRT19 and GRP. Conclusion: The approach adopted is feasible to screen for new tumour specific promoters with biomarkers. In addition, the screened lung-specific promoters might have potential for use in lung cancer targeted gene therapy research.

Synergistic Penetration of Ethosomes and Lipophilic Prodrug on the Transdermal Delivery of Acyclovir

Yan Zhou,Yu-Hui Wei,Guo-Qiang Zhang,Xin-An Wu 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.4

The aim of this study was to investigate the lipophilic prodrug as a means of promoting acyclovir (ACV) that exhibited biphasic insolubility into the ethosomes for optimum skin delivery. Acyclovir Palmitate (ACV-C16) was synthesized as the lipophilic prodrug of ACV. The ethosomal system and the liposomal system bearing ACV or ACV-C16 were prepared, respectively. The systems were characterized for shape, zeta potential value, particle size, and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy were used for the percutaneous absorption studies. The results showed that the entrapment efficiency of ACV-C16ethosomes (87.75%) were much higher than that of ACV ethosomes (39.13%). The quantity of drug in the skin from ACV-C16 ethosomes at the end of the 24 h transdermal experiment (622.89 μg/cm2) was 5.30 and 3.43 times higher than that from ACV-C16 hydroalcoholic solution and ACV ethosomes, respectively. This study indicated that the binary combination of the lipophilic prodrug ACV-C16 and the ethosomes synergistically enhanced ACV absorption into the skin.

Quercetin Attenuates Visceral Hypersensitivity and 5-Hydroxytryptamine Availability in Postinflammatory Irritable Bowel Syndrome Rats: Role of Enterochromaffin Cells in the Colon

Hong-Yan Qin,Kai-hong Zang,Xiao Zuo,Xin-An Wu,Zhaoxiang Bian 한국식품영양과학회 2019 Journal of medicinal food Vol.22 No.7

Intestinal enterochromaffin (EC) cell hyperplasia and increased 5-hydroxytryptamine (5-HT) availability play key roles in the pathogenesis of abdominal hypersensitivity of irritable bowel syndrome (IBS). This study aims to study the effect of quercetin on visceral pain and 5-HT availability in postinflammatory IBS (PI-IBS) rats. PI-IBS model rats were administered quercetin by gavage at doses of 5, 10, and 20 mg/kg for 14 days. Compared with normal rats, the visceral pain threshold of PI-IBS rats was markedly decreased and the abdominal motor response to colon distension was markedly increased. The EC cell count and 5-HT level, as well as tryptophan hydroxylase (TPH) protein, were all significantly elevated in PI-IBS rats, while the 5-HT reuptake transporter (serotonin transporter) was reduced. Genes that are responsible for enteroendocrine cell differentiation, that is, Ngn3 and pdx1, were significantly increased in the PI-IBS group. Quercetin treatment markedly elevated the pain threshold pressure and decreased the visceral motor response of PI-IBS animals; and EC cell density and 5-HT level, as well as TPH expression, in the PI-IBS group were all reduced by quercetin. Quercetin treatment also significantly reduced colonic expression of Ngn3 and pdx1 of PI-IBS. Findings from the present study indicated that the analgesic effect of quercetin on PI-IBS may result from reduction of 5-HT availability in the colon, and the regulatory role of quercetin in endocrine progenitors may contribute to reduced EC cells.

Design of 2-DOF decoupled large stroke precision positioning platform

Hua-wei Ji,Bo Lv,Tian-yi Li,Fan Yang,An-qi Qi,Xin Wu,Jing Ni 대한기계학회 2022 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.36 No.12

Aiming at the problem that the output displacement of the piezoelectric actuator is small and the coupling motion of the positioning platform affects the positioning accuracy, we designed a 2-DOF decoupling large-stroke precision positioning platform. First, a dynamic model based on the lumped mass method was established and verified by simulation. The multi-objective genetic optimization algorithm was used to optimize the structural size parameters of the positioning platform, and the optimal solution set of the structural size parameters of the positioning platform was obtained. Finally, according to the theoretical and simulation results, a prototype was fabricated and the working stroke, decoupling performance and natural frequency were tested experimentally. The results show the coupling rates between axes of the positioning platform in the x-direction and y-direction are 1.31 % and 1.62 %, respectively, the natural frequency is 337.2 Hz, and the positioning stroke is 89.2 μm×85.9 μm. The positioning platform designed in this paper is decoupled and has a large output stroke.