Enhanced targeted drug delivery through controlled release in a three-dimensional vascular tree

Area of Science:

• Biomedical Engineering
• Computational Fluid Dynamics
• Pharmacology

Background:

• Optimizing drug delivery to specific targets within the vasculature is crucial for therapeutic efficacy.
• Current methods for determining optimal injection sites are limited, especially in complex 3D geometries.
• Particle release score map (PRSM) and transient particle release score map (TPRSM) offer a novel approach for controlled particle release and targeting.

Purpose of the Study:

• To investigate the feasibility of precise drug targeting in a complex 3D vascular tree model.
• To determine optimal drug injection locations for enhanced target efficiency (TE) under realistic hemodynamic conditions.
• To evaluate the influence of steady and pulsatile flow on particle release strategies.

Main Methods:

• Utilized a 3D vascular tree geometry with Poiseuille and Womersley velocity profiles for steady and pulsatile flow simulations, respectively.
• Modeled blood's non-Newtonian shear-thinning behavior using the Carreau-Yasuda model.
• Employed a one-way coupled Eulerian-Lagrangian particle tracking method to simulate drug particle trajectories.

Main Results:

• Particle size and density had minimal impact on drug particle trajectories.
• The optimal release scoring algorithm identified multiple optimal release locations under steady flow.
• A single, unique optimal release location was identified under pulsatile flow conditions.
• An average target efficiency of 66% was achieved in pulsatile flow simulations.

Conclusions:

• The proposed particle release and targeting technique shows promise for optimizing drug delivery in complex vascular networks.
• The study highlights the importance of flow dynamics (steady vs. pulsatile) in determining optimal injection strategies.
• Further mathematical modeling refinement and experimental validation are warranted to advance this in silico approach.