Platelet-inspired microparticles for targeted drug delivery to the atherosclerotic plaque
File(s)
Author(s)
Hu, Yangshuo
Type
Thesis
Abstract
Atherosclerosis is a leading cause of coronary heart disease, characterised by chronic arterial inflammation and the development of occlusive lipid plaques. Current treatments rely primarily on systemic administration of lipid-lowering agents and antiplatelet drugs, but these are often associated with significant side effects, highlighting the need for more specific and localised therapeutic approaches. Platelets naturally attach to vessel injuries. This thesis presents the development of a gelatin microparticle (GMP) platform designed to mimic platelet adhesion and target atherosclerotic plaques. To efficiently assess the adhesion of particles in an atherosclerotic environment in vitro, a microfluidic model recapitulating the physical and biochemical environment of atherosclerosis was developed. The device recapitulated a central pathophysiological event, the elongation of von Willebrand factor (vWF) under high shear stress and successfully demonstrated platelet rolling and capture. A gelatin based microparticle was formulated on a water-in-oil emulsion based protocol, which demonstrated deformability, compared to rigid polystyrene particles. The gelatin microparticles could adhere specifically to vWF within the atherosclerosis chip, under high shear flow.
Furthermore, proof-of-concept drug encapsulation and release experiments showed that GMPs achieved high loading efficiency and exhibited enhanced release under shear stimulation, consistent with their deformable nature. A bio-fabricated lymphatic construct was developed in parallel, demonstrating how similar systems could be applied to probe the role of mechanical cues, such as matrix stiffness and cyclic stretching, in regulating vascular drug delivery. Together, these results demonstrate the promise of gelatin microparticles as a drug delivery system tailored for the haemodynamic and biochemical environment of atherosclerosis. Beyond establishing a platform for plaque-targeted therapy, this work also establishes a foundation for exploring how mechanical cues such as shear stress, stiffness, and cyclic strain could influence vascular drug delivery strategies.
Furthermore, proof-of-concept drug encapsulation and release experiments showed that GMPs achieved high loading efficiency and exhibited enhanced release under shear stimulation, consistent with their deformable nature. A bio-fabricated lymphatic construct was developed in parallel, demonstrating how similar systems could be applied to probe the role of mechanical cues, such as matrix stiffness and cyclic stretching, in regulating vascular drug delivery. Together, these results demonstrate the promise of gelatin microparticles as a drug delivery system tailored for the haemodynamic and biochemical environment of atherosclerosis. Beyond establishing a platform for plaque-targeted therapy, this work also establishes a foundation for exploring how mechanical cues such as shear stress, stiffness, and cyclic strain could influence vascular drug delivery strategies.
Version
Open Access
Date Issued
2025-10-04
Date Awarded
01/02/2026
License URL
Advisor
Celiz, Adam
Sponsor
Imperial College London
Publisher Department
Department of Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)