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Mathematical Biology Seminar

 

 

Tuesday, 04/09/2019, at 4:10 - 5:00

 

 

SPARK 327

 

 

 

 

Stochastic modeling and simulations of targeted drug delivery across blood-brain barrier using nanoparticles

 

Jin Liu

Associate Professor

 

 

School of Mechanical and Materials Engineering, WSU

 

 

 

 

 

Abstract

 

 

 

The existence of the blood-brain barrier (BBB) makes the treatment of brain diseases significantly challenging. Delivery of drug-loaded carriers (nanoparticles) across BBB through receptor-mediated transcytosis (RMT) is noninvasive and effective strategy to overcome the challenge. During RMT, the nanoparticles actively interact with the membrane and the membrane profle involves extreme deformations during particle internalization and expulsion. Recently we have developed a stochastic model to study the endocytosis and exocytosis during nanoparticles across BBB. The model is based on the combination of a stochastic particle binding model with a membrane model, and accounts for both the clathrin-mediated endocytosis at the blood side and the actin-mediated exocytosis at the brain side. Our results showed the particle must have certain avidity with enough antibody density and antibody-receptor binding affinity to enter the BBB at blood side, while too much avidity limited the particle release from the brain side. We have also explored the functional roles of actin during exocytosis. Our simulations indicated that the membrane compression due to the actin induced tension tended to break the antibody-receptor bonds and to shrink the fusion pore. Therefore, an intermediate tension promoted the fusion pore expansion and particle release, while high tension prohibits particle release. The model is able to provide mechanistic insights into RMT, and represents a powerful platform for aiding the rational design of drug carriers for transcellular drug delivery.