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        Pharmacokinetics and Biodistribution of Surface Modification Polymeric Nanoparticles

        Liu, Mingxing,Li, Huifang,Luo, Guoan,Liu, Qingfei,Wang, Yiming 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.4

        The objective of this study is to investigate the pharmacokinetics and biodistribution of free breviscapine (BVP) and coated BVP-loaded poly (D, L-lactic acid) nanoparticles (BVP-PLA-NPs) in rats after i.v. administration. Coated BVP-PLA-NPs were prepared by the spontaneous emulsification solvent diffusion method and characterized. The BVP content in the NPs, the biological samples and in vitro release was measured by the high-performance liquid chromatography (HPLC). The mean sizes of coated BVP-PLA-NPs were 177 and 319 nm with a narrow distribution and smooth sphere shapes, entrapment efficiency of 86.9% and 93.1%, respectively. Drug release profiles in phosphate buffer and plasma exhibited a biphasic release phenomenon. After i.v. administration of free BVP and NPs suspensions in rats, area under plasma concentration-time curve and elimination $t_{1/2}$ were increased 9.3-fold and 10.9-fold for 177 nm of NPs, and 4.4-fold and 17.1-fold for 319 nm of NPs compared with that of free BVP, respectively. NPs were mainly distributed in liver, spleen, heart and brain. In addition, NPs could penetrate blood brain barrier (BBB) and the particle size had some effect on pharmacokinetics and biodistribution. Coated BVP-PLA-NPs could effectively avoid the capture by the reticuloendothelial system and prolong the half-life of BVP. Moreover, these NPs could penetrate BBB and enhance the accumulation of BVP in brain.

      • KCI등재

        Pharmacokinetics and Biodistribution of Surface Modification Polymeric Nanoparticles

        Mingxing Liu,Huifang Li,Guoan Luo,Qingfei Liu,Yiming Wang 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.4

        The objective of this study is to investigate the pharmacokinetics and biodistribution of free breviscapine (BVP) and coated BVP-loaded poly (D, L-lactic acid) nanoparticles (BVP-PLANPs) in rats after i.v. administration. Coated BVP-PLA-NPs were prepared by the spontaneous emulsification solvent diffusion method and characterized. The BVP content in the NPs, the biological samples and in vitro release was measured by the high-performance liquid chromatography (HPLC). The mean sizes of coated BVP-PLA-NPs were 177 and 319 nm with a narrow distribution and smooth sphere shapes, entrapment efficiency of 86.9% and 93.1%, respectively. Drug release profiles in phosphate buffer and plasma exhibited a biphasic release phenomenon. After i.v. administration of free BVP and NPs suspensions in rats, area under plasma concentration-time curve and elimination t1/2 were increased 9.3-fold and 10.9-fold for 177 nm of NPs, and 4.4-fold and 17.1-fold for 319 nm of NPs compared with that of free BVP, respectively. NPs were mainly distributed in liver, spleen, heart and brain. In addition, NPs could penetrate blood brain barrier (BBB) and the particle size had some effect on pharmacokinetics and biodistribution. Coated BVP-PLA-NPs could effectively avoid the capture by the reticuloendothelial system and prolong the half-life of BVP. Moreover, these NPs could penetrate BBB and enhance the accumulation of BVP in brain.

      • KCI등재

        A Microfluidic Hydrogel Chip with Orthogonal Dual Gradients of Matrix Stiffness and Oxygen for Cytotoxicity Test

        Weixing Wang,Lili Li,Mingyu Ding,Guoan Luo,Qionglin Liang 한국바이오칩학회 2018 BioChip Journal Vol.12 No.2

        The oxygen tensions and matrix stiffness play important roles in regulating cell response to cytotoxic drugs. In recent years, single spatiotemporal oxygen or matrix stiffness gradient has been established by various technologies for cell studies. However, the synergistic effects of the two factors on tumor cells remained elusive. In this study, we created a highly integrated and easy-to-operate microfluidic device. It was capable of generating more continuous, linear, stable and diffusive hydrogel stiffness gradient over a well-defined oxygen gradient. Sodium hydroxide and pyrogallol were used to scavenge oxygen and generate oxygen gradient, skillfully avoiding the utilization of bulky pressurized gas cylinders and sophisticated flow control by conventional methods. Utilizing the newly developed microfluidic device, we successfully performed drug test with a hypoxia sensitive anti-cancer drug, triapazamine (TPZ), on A549 cells under perpendicular construction of oxygen and spatially hydrogel stiffness gradients. The cell experiment results demonstrated the matrix stiffness-dependent cell drug resistance and hypoxia-induced cytotoxicity of TPZ. In summary, the developed microfluidic device exhibits high potential in the study of matrix stiffness-dependent cell responses and oxygen-sensitive drug cytotoxicity. Furthermore, the design principle can be functionally extended to other dual factors system and will facilitate the study of cell response in complex physiological and pathological conditions.

      • KCI등재후보

        A droplet-based microfluidic device for long-term culture and longitudinal observation of Caenorhabditis elegans

        Dawei Ying,Kai Zhang,Naipeng Li,Xiaoni Ai,Qionglin Liang,Yiming Wang,Guoan Luo 한국바이오칩학회 2012 BioChip Journal Vol.6 No.3

        A droplet-based microfluidic device for long-term culture and longitudinal observation of Caenorhabditis eleganswas presented. The worms were encapsulated in W/O droplets and controllably introduced into separate chambers, where the medium/oil or medium/air interface can be manipulated by a gravity -actuated technique, for lifelong culture. This device also contained clamp structures for reversibly immobilization of each worm separately, and thus we were able to track more details about each worm. Several phenotypes of worms were monitored from their fourth larva stage to death. The relationship between worm body length, stroke frequency and lifespan with this device was then studied. This device had a potential in various longitudinal researches on C. elegans including aging, drug screening, toxicity evaluation and etc.

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