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

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Zhou Y, Zhang G, Rao Z, Yang Y, Zhou Q, Qin H, Wei Y, Wu X

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

Arch Pharm Res. 2015 Jul;38(7):1325-35. doi: 10.1007/s12272-014-0539-6. Epub 2015 Jan 8.

PubMed ID

25567760 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Venlafaxine	P-glycoprotein 1	Protein	Humans	Unknown	Substrate Inhibitor	Details