Abstract
Delivery of drugs across Blood-brain barrier (BBB) can be enhanced by physical stimulation (e.g. ultrasound). When BBB is opened by ultrasound sonication in the presence of microbubbles, its vascular permeability will decay due to BBB repairing. The transport and accumulation of nanodrugs in brain tissue is affected by both physicochemical properties of drugs and closure dynamics of BBB. In this study, we developed a mathematical model and employed animal experiments to investigate the impact of recovery of disrupted BBB on nanodrug delivery into brain tissue. We chose Evans blue (EB)-albumin complexes as a model nanodrug and studied the effects of initial permeability, decaying speed of permeability and half-life of EB-albumin complexes on their spatial-temporal concentration response and accumulation in brain tissue. The transport parameters used in this model were obtained from previously published studies and the fitting of our experimental data with Particle Swarm Optimization (PSO). The simulation results showed that there exists optimal initial permeability and decaying speed of permeability to achieve a maximum AUC (area under the concentration-time curve) of EB-albumin in the brain tissue. The results indicate that we can enhance the accumulation of nanodrugs safely in brain tissue by controlling the recovery dynamics of BBB opening.
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