title: Design of asymmetric particles containing a charged interior and a neutral surface charge: comparative study on in vivo circulation of polyelectrolyte microgels.
abstract: Lowering the modulus of hydrogel particles could enable them to bypass in vivo physical barriers that would otherwise filter particles with similar size but higher modulus. Incorporation of electrolyte moieties into the polymer network of hydrogel particles to increase the swelling ratio is a straightforward and quite efficient way to decrease the modulus. In addition, charged groups in hydrogel particles can also help secure cargoes. However, the distribution of charged groups on the surface of a particle can accelerate the clearance of particles. Herein, we developed a method to synthesize highly swollen microgels of precise size with near-neutral surface charge while retaining interior charged groups. A strategy was employed to enable a particle to be highly cross-linked with very small mesh size, and subsequently PEGylated to quench the exterior amines only without affecting the internal amines. Acidic degradation of the cross-linker allows for swelling of the particles to microgels with a desired size and deformability. The microgels fabricated demonstrated extended circulation in vivo compared to their counterparts with a charged surface, and could potentially be utilized in in vivo applications including as oxygen carriers or nucleic acid scavengers.
authors.affiliation: Department of Chemistry, ‡Lineberger Comprehensive Cancer Center, §Institute for Nanomedicine, ∥School of Pharmacy, ⊥Department of Pathology and Laboratory Medicine, #Institute for Advanced Materials, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.forename: Shaomin
authors.initials: S
authors.lastname: Tian
authors.forename: Jay S
authors.initials: JS
authors.lastname: Raval
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000588:Amines / Q000737:chemistry; D001802:Blood Substitutes; D002470:Cell Survival / Q000187:drug effects; D003432:Cross-Linking Reagents; D004573:Electrolytes / Q000737:chemistry*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011247:Pregnancy; D013499:Surface Properties
chemical_list: D000588:Amines; D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D004573:Electrolytes; D020100:Hydrogels; D011092:Polyethylene Glycols