Nanoparticle Mediated P-Glycoprotein Silencing for Improved Drug Delivery across the Blood-Brain Barrier: A siRNA-Chitosan Approach

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.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-01-23

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1371/journal.pone.0054182PMID 23372682PMCID 3553124
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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