title: Signaled drug delivery and transport across the blood-brain barrier.
abstract: We use a mathematical model to describe the delivery of a drug to a specific region of the brain. The drug is carried by liposomes that can release their cargo by application of focused ultrasound (US). Thereupon, the drug is absorbed through the endothelial cells that line the brain capillaries and form the physiologically important blood-brain barrier (BBB). We present a compartmental model of a capillary that is able to capture the complex binding and transport processes the drug undergoes in the blood plasma and at the BBB. We apply this model to the delivery of levodopa (L-dopa, used to treat Parkinson's disease) and doxorubicin (an anticancer agent). The goal is to optimize the delivery of drug while at the same time minimizing possible side effects of the US.
authors.affiliation: a Department of Mathematical Sciences , University of Wisconsin , Milwaukee , WI , USA .
authors.forename: Peter
authors.initials: P
authors.lastname: Hinow
authors.affiliation: b Department of Mathematics , Pomona College , Claremont , CA , USA .
authors.forename: Ami
authors.initials: A
authors.lastname: Radunskaya
authors.affiliation: c Department of Chemistry , University of Otago , Dunedin , New Zealand .
authors.forename: Sean M
authors.initials: SM
authors.lastname: Mackay
authors.affiliation: d Department of Anatomy and the Brain Health Research Centre , University of Otago , Dunedin , New Zealand .
authors.forename: John N J
authors.initials: JN
authors.lastname: Reynolds
authors.affiliation: e Department of Biology , University of Oregon , Eugene , OR , USA , and.
authors.forename: Morgan
authors.initials: M
authors.lastname: Schroeder
authors.affiliation: c Department of Chemistry , University of Otago , Dunedin , New Zealand .
authors.forename: Eng Wui
authors.initials: EW
authors.lastname: Tan
authors.affiliation: f New Zealand's National School of Pharmacy, University of Otago , Dunedin , New Zealand.
authors.forename: Ian G
authors.initials: IG
authors.lastname: Tucker
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008958:Models, Molecular
chemical_list: D007980:Levodopa; D004317:Doxorubicin
keywords: Focused ultrasound; liposomal delivery; mathematical modeling