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        Pharmacokinetics and Biodistribution of Paclitaxel-Ioaded Pluronic P105 Polymeric Micelles

        Wang, Yongzhong,Li, Yajuan,Zhang, Lijun,Fang, Xiaoling 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.4

        A novel polymeric micelle formulation of paclitaxel (PTX) has been prepared with the purpose of improving in vitro release as well as prolonging the blood circulation time of PTX in comparison to a current PTX formulation, Taxol injection. This work was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of PTX-loaded Pluronic P105 micellar system. The micelles were prepared by thin-film method using a nonionic surfactant Pluronic P105 and a hydrophobic anticancer drug, PTX. With a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 24 nm with narrow size distribution and a spherical shape. The in vitro release profiles indicated that the release of PTX from the micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic study in rats, in which $t_{1/2{\beta}}$ and AUC of the micelle formulation were 4.9 and 5.3-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTX-loaded micelles not only decreased drug uptake by liver, but also prolonged drug retention in blood and increased distribution of drug in lung, spleen and kidney. These results suggested that the P105 polymeric micelles may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for i.v. administration of PTX.

      • KCI등재

        Pharmacokinetics and Biodistribution of Paclitaxel-loaded Pluronic P105 Polymeric Micelles

        Yongzhong Wang,Yajuan Li,Lijun Zhang,Xiaoling Fang 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.4

        A novel polymeric micelle formulation of paclitaxel (PTX) has been prepared with the purpose of improving in vitro release as well as prolonging the blood circulation time of PTX in comparison to a current PTX formulation, Taxol injection. This work was designed to investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of PTX-loaded Pluronic P105 micellar system. The micelles were prepared by thin-film method using a nonionic surfactant Pluronic P105 and a hydrophobic anticancer drug, PTX. With a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 24 nm with narrow size distribution and a spherical shape. The in vitro release profiles indicated that the release of PTX from the micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic study in rats, in which t1/2β and AUC of the micelle formulation were 4.9 and 5.3-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTXloaded micelles not only decreased drug uptake by liver, but also prolonged drug retention in blood and increased distribution of drug in lung, spleen and kidney. These results suggested that the P105 polymeric micelles may efficiently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for i.v. administration of PTX.

      • KCI등재

        Increase in Hypotonic Stress-Induced Endocytic Activity in Macrophages via ClC-3

        Yan, Yutao,Ding, Yu,Ming, Bingxia,Du, Wenjiao,Kong, Xiaoling,Tian, Li,Zheng, Fang,Fang, Min,Tan, Zheng,Gong, Feili Korean Society for Molecular and Cellular Biology 2014 Molecules and cells Vol.37 No.5

        Extracellular hypotonic stress can affect cellular function. Whether and how hypotonicity affects immune cell function remains to be elucidated. Macrophages are immune cells that play key roles in adaptive and innate in immune reactions. The purpose of this study was to investigate the role and underlying mechanism of hypotonic stress in the function of bone marrow-derived macrophages (BMDMs). Hypotonic stress increased endocytic activity in BMDMs, but there was no significant change in the expression of CD80, CD86, and MHC class II molecules, nor in the secretion of TNF-${\alpha}$ or IL-10 by BMDMs. Furthermore, the enhanced endocytic activity of BMDMs triggered by hypotonic stress was significantly inhibited by chloride channel-3 (ClC-3) siRNA. Our findings suggest that hypotonic stress can induce endocytosis in BMDMs and that ClC-3 plays a central role in the endocytic process.

      • KCI등재

        Increase in Hypotonic Stress-Induced Endocytic Activity in Macrophages via ClC-3

        Yutao Yan,Yu Ding,Bingxia Ming,Wenjiao Du,Xiaoling Kong,Li Tian,Fang Zheng,Min Fang,Zheng Tan,Feili Gong 한국분자세포생물학회 2014 Molecules and cells Vol.37 No.5

        Extracellular hypotonic stress can affect cellular function. Whether and how hypotonicity affects immune cell function remains to be elucidated. Macrophages are immune cells that play key roles in adaptive and innate in immune reactions. The purpose of this study was to investigate the role and underlying mechanism of hypotonic stress in the function of bone marrow-derived macrophages (BMDMs). Hypotonic stress increased endocytic activity in BMDMs, but there was no significant change in the expression of CD80, CD86, and MHC class II molecules, nor in the secretion of TNF- or IL-10 by BMDMs. Furthermore, the enhanced endocytic activity of BMDMs triggered by hypotonic stress was significantly inhibited by chloride channel-3 (ClC-3) siRNA. Our findings suggest that hypotonic stress can induce endocytosis in BMDMs and that ClC-3 plays a central role in the endocytic process.

      • KCI등재

        Enhanced Transfection of Polyplexes Based on Pluronic-Polypropylenimine Dendrimer for Gene Transfer

        Junguo Hao,Yuanjia Tang,Xianyi Sha,Ye Jiang,Zhiwen Zhang,Wei Zhang,Yajuan Li,Xiaoling Fang 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.7

        Third generation cationic dendritic polymeric polypropyleneimine (PPI) was modified by Pluronic P123 and investigated for gene delivery. The cytotoxicity of P123-PPI was evaluated by the MTT assay and shown to be much lower than that of PPI alone. P123-PPI and PPI can both condense plasmid DNA into nanoparticles with a size of approximately 100 nm and a zeta potential of about 15 mV at the N/P ratio 20:1. The nanoparticles can protect plasmid DNA from being digested by DNase I at a concentration of 0.4 U/μg DNA. The nanoparticles were resistant to dissociation induced by 50% fetal bovine serum and 75 μg/mL sodium heparin. The transfection efficiency of SPC-A1 cells using P123-PPI/DNA nanoparticles was much higher than the transfection utilizing PPI/DNA nanoparticles. The addition of free P123 during the preparation of P123-PPI/DNA nanoparticles could significantly enhance the transfection efficiency in the presence of 10% fetal bovine serum. Therefore, P123-PPI/DNA complex nanoparticles may be a safe, efficient and promising cationic conjugate for gene delivery.

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