Mohamadamin Forouzandehmehr and Amir Shamloo*
Background: The continuing inflammatory response entailed by atherosclerosis is categorised by a pathological surface expression of certain proteins over the endothelium, namely, P-selectins. Thus, to boost the efficiency of drug carriers these proteins can be used as binding targets.
Method: An in-silico patient-specific model of a Left Anterior Descending (LAD) artery considering the luminal unevenness was built and meshed using the finite element method.
Objectives: Delivery of particles in a specific size range, from 200 to 3200 nm, covered by P-selectin aptamers (PSA), to an atherosclerotic plaque in a pathologically high haematocrit (Hct) blood flow was simulated. The surface of the plaque was assumed to possess a pathologically high expression of P-Selectins.
Results: The distribution of deposited particles over the plaque, in high Hct blood, was significantly more homogenous compared to that of particles travelled in normal blood Hct. Moreover, in the high Hct, the increase in the particle size, from 800 nm forwards, had a trivial effect on the upsurge in the surface density of adhered particles (SDAs) over the targeted endothelium. Yet, in normal blood Hct (45% in this research) the increase in the particle diameter from 800 nm forwards resulted in a significant increase in the SDAs over the targeted plaque. Interestingly, unlike the adsorption pattern of particles in normal Hct, a significant distribution of deposited particles in the post-constriction region of the atherosclerotic plaque was observed.
Conclusion: Our findings lend insights into designing optimum carriers of anti-thrombotic/inflammatory drugs specifically for high blood Hct conditions.
High haematocrit, nano drug carriers, adhesion, personalised modelling, atherosclerotic plaque, SDA.
School of Mechanical Engineering, Sharif University of Technology, Tehran, School of Mechanical Engineering, Sharif University of Technology, Tehran