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.

• Focused ultrasound
• liposomal delivery
• mathematical modeling

Acknowledgements

We acknowledge the kind hospitality of the University of Otago during several collaborative visits and during a sabbatical stay of Ami Radunskaya.

Declaration of interest

The authors declare no conflict of interest. We are grateful for financial support from the grant “Collaborative Research: Predicting the Release Kinetics of Matrix Tablets” (DMS 1016214 to Peter Hinow and DMS 1016136 to Ami Radunskaya) of the National Science Foundation of the United States of America. Morgan Schroeder received an award from the Support for Undergraduate Research Fellows (SURF) program at the University of Wisconsin – Milwaukee. John Reynolds received a Rutherford Discovery Fellowship from the Royal Society of New Zealand. Sean Mackay received a doctoral scholarship from the University of Otago. Peter Hinow was partly supported from the Simons Foundation grant “Collaboration on Mathematical Biology” during a visit to Pomona College. The funding bodies had no influence on study design, collection, analysis and interpretation of data.