Abstract
Vascular-targeted drug carriers must localize to the wall (i.e., marginate) and adhere to a diseased endothelium to achieve clinical utility. The particle size has been reported as a critical physical property prescribing particle margination in vitro and in vivo blood flows. Different transport process steps yield conflicting requirements-microparticles are optimal for margination, but nanoparticles are better for intracellular or tissue delivery. Here, we evaluate deformable hydrogel microparticles as carriers for transporting nanoparticles to a diseased vascular wall. Depending on microparticle modulus, nanoparticle-loaded poly(ethylene glycol)-based hydrogel microparticles delivered significantly more 50-nm nanoparticles to the vessel wall than freely injected nanoparticles alone, resulting in >3000% delivery increase. This work demonstrates the benefit of optimizing microparticles' efficient margination to enhance nanocarriers' transport to the vascular wall.
Highlights
Vascular-targeted drug carriers (VTCs) are typically polymeric particles engineered to adhere to and accumulate at sites of disease via markers on the vascular wall, producing localized delivery of drugs
We evaluated the importance of poly(ethylene glycol) (PEG) diacrylate (PEGDA) precursor’s molecular weight and composition in the final NP loading into hydrogel MPs
Previous works have suggested that the low nanocarrier accumulation is linked to inefficient margination, where carriers sized 500 nm or less are entrapped within the red blood cell core and fail to distribute to the vascular wall in vessels of up to 2 mm size [13, 29]
Summary
Vascular-targeted drug carriers (VTCs) are typically polymeric particles engineered to adhere to and accumulate at sites of disease via markers on the vascular wall, producing localized delivery of drugs. The ability of the targeting ligands grafted on carrier surfaces to bind overexpressed receptors on the diseased vascular wall has been debated in the literature; ligands are often proteins, which are thought to decrease the circulation time and half-lives of particles significantly [17, 18]. Some use this fact alone as a rationale to abandon the targeted particle strategy, focusing instead on extending the circulation time for passive accumulation. These competing paradigms have yet to be directly tested experimentally
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