Vascular-targeted drug delivery using micro/nano-particles as drug carriers have been exploited in recent years in therapeutic interventions of cancer, cardiovascular, pulmonary and inflammatory diseases and so on. This approach has numerous advantages over conventional delivery (e.g. lower drug dosage and thus reduced side effects, sustained release), however, a major challenge is to improve cell selectivity and wall-adhesion efficiency by functionalizing the drug carriers. Extensive research has focused on identifying disease-associated biomolecules on the endothelium, or suitable antibody/peptides targeting these molecules, however, much less attention has been paid to a crucial haemodynamic aspect: will the drug carriers be able to migrate from the midstream of the blood to the RBC-free layer close to the vessel wall, under complex interactions with blood cells? This is particularly important in small arteries, where many diseases (e.g. arteriolosclerosis) develop but surgical operations become difficult. The aim of the present project is therefore to conduct a systematic study of the effects of system parameters, such as the blood flow condition, the particle shape, size etc on the cross-stream migration and margination of microparticles in blood flows in small arteries.
Specific research objectives are: 1, to develop experimental and computational platform to study the cross-stream migration and margination of microcapsules in blood flow in small arteries; 2, to investigate the effects of system parameters, such as the shape and size of the capsule, the flow inertia and shear rates, vessel geometry etc. on margination of microcapsules in blood flows; 3, to develop practical principles for engineering microcapsules with optimum margination in blood flow in small arteries. All three research objectives have been largely achieved during the fellowship period.
