Deformable microparticles for shuttling nanoparticles to the vascular wall

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.

pH-Triggered Assembly of Endomembrane Multicompartments in Synthetic Cells

“…By entrapping various stimuli-responsive compartments, minimal cross-reactivity and control over the release sequence could be embedded within a single synthetic eukaryote. The assembly of such an endomembrane system within a micron-scale carrier could be engineered to release therapeutics through the vascular walls, 59 while enabling improved functionality, reduced passive leakage, cross-reactivity, and flexibility to name a few.…”

Biophysical targeting of high‐risk cerebral aneurysms

“…However, while the particles we have used in this study are not intended for use in a clinical setting, there are several ways to implement such micron or sub-micron sized carriers while minimizing the potential limitations and the filtering effects of relatively large carriers. One of the ways is the use of deformable carriers that mimic the physics of the red blood cells, which has been shown to increase circulation time and reduce accumulation of carriers within the lung and liver as well as reduce patient toxicity 42,43 .…”

“…One of the ways is the use of deformable carriers that mimic the physics of the red blood cells, which has been shown to increase circulation time and reduce accumulation of carriers within the lung and liver as well as reduce patient toxicity. 42 , 43 Additionally, RBC‐based drug carriers have recently shown a remarkable improvement in targeting lung and other organs. 44 Furthermore, such RBC carriers can be made to adhere to exposed collagen, 45 are about 10 μm in diameter and have relatively long circulation time, and thus could potentially be valuable for targeting high‐risk brain aneurysms.…”

Mechanical characterization of soft microparticles prepared by droplet microfluidics

“…They presented that there is an optimal stiffness value for the particles with high margination probabilities based on the adhesion strength 81 . Fish et al 82 also employed nanoparticle‐loaded PEGDA microparticles in a blood vessel model for the optimization of microparticle modulus for efficient margination and nanoparticle delivery.…”