title: Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles.
abstract: It has long been hypothesized that elastic modulus governs the biodistribution and circulation times of particles and cells in blood; however, this notion has never been rigorously tested. We synthesized hydrogel microparticles with tunable elasticity in the physiological range, which resemble red blood cells in size and shape, and tested their behavior in vivo. Decreasing the modulus of these particles altered their biodistribution properties, allowing them to bypass several organs, such as the lung, that entrapped their more rigid counterparts, resulting in increasingly longer circulation times well past those of conventional microparticles. An 8-fold decrease in hydrogel modulus correlated to a greater than 30-fold increase in the elimination phase half-life for these particles. These results demonstrate a critical design parameter for hydrogel microparticles.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Merkel
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Jones
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Herlihy
authors.forename: Farrell R
authors.initials: FR
authors.lastname: Kersey
authors.forename: Adam R
authors.initials: AR
authors.lastname: Shields
authors.forename: Mary
authors.initials: M
authors.lastname: Napier
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.forename: Huali
authors.initials: H
authors.lastname: Wu
authors.forename: William C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: Andrew Z
authors.initials: AZ
authors.lastname: Wang
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D032701:Biomimetics; D004337:Drug Carriers / Q000737:chemistry; D004867:Equipment Design; D004912:Erythrocytes / Q000166:cytology*; D005260:Female; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007700:Kinetics; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence / Q000379:methods; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate