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KMID : 0043320150380071325
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Archives of Pharmacal Research
2015 Volume.38 No. 7 p.1325 ~ p.1335
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Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp
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Zhou Yan
Zhang Guoqiang
Rao Zhi
Yang Yang
Zhou Qian
Qin Hongyan
Wei Yuhui
Wu Xin’an
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Abstract
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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.
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KEYWORD
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P-glycoprotein, Blood?brain barrier, Solid lipid nanoparticles, Venlafaxine
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