Nanoparticle Mediated P-Glycoprotein Silencing for Improved Drug Delivery across the Blood-Brain Barrier: A siRNA-Chitosan Approach
2013 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 8, no 1, e54182- p.Article in journal (Refereed) Published
The blood-brain barrier (BBB), composed of tightly organized endothelial cells, limits the availability of drugs to therapeutic targets in the central nervous system. The barrier is maintained by membrane bound efflux pumps efficiently transporting specific xenobiotics back into the blood. The efflux pump P-glycoprotein (P-gp), expressed at high levels in brain endothelial cells, has several drug substrates. Consequently, siRNA mediated silencing of the P-gp gene is one possible strategy how to improve the delivery of drugs to the brain. Herein, we investigated the potential of siRNA-chitosan nanoparticles in silencing P-gp in a BBB model. We show that the transfection of rat brain endothelial cells mediated effective knockdown of P-gp with subsequent decrease in P-gp substrate efflux. This resulted in increased cellular delivery and efficacy of the model drug doxorubicin.
Place, publisher, year, edition, pages
2013. Vol. 8, no 1, e54182- p.
IdentifiersURN: urn:nbn:se:umu:diva-66796DOI: 10.1371/journal.pone.0054182ISI: 000314021500036OAI: oai:DiVA.org:umu-66796DiVA: diva2:610335