title: Plasma protein corona modulates the vascular wall interaction of drug carriers in a material and donor specific manner.
abstract: The nanoscale plasma protein interaction with intravenously injected particulate carrier systems is known to modulate their organ distribution and clearance from the bloodstream. However, the role of this plasma protein interaction in prescribing the adhesion of carriers to the vascular wall remains relatively unknown. Here, we show that the adhesion of vascular-targeted poly(lactide-co-glycolic-acid) (PLGA) spheres to endothelial cells is significantly inhibited in human blood flow, with up to 90% reduction in adhesion observed relative to adhesion in simple buffer flow, depending on the particle size and the magnitude and pattern of blood flow. This reduced PLGA adhesion in blood flow is linked to the adsorption of certain high molecular weight plasma proteins on PLGA and is donor specific, where large reductions in particle adhesion in blood flow (>80% relative to buffer) is seen with ∼60% of unique donor bloods while others exhibit moderate to no reductions. The depletion of high molecular weight immunoglobulins from plasma is shown to successfully restore PLGA vascular wall adhesion. The observed plasma protein effect on PLGA is likely due to material characteristics since the effect is not replicated with polystyrene or silica spheres. These particles effectively adhere to the endothelium at a higher level in blood over buffer flow. Overall, understanding how distinct plasma proteins modulate the vascular wall interaction of vascular-targeted carriers of different material characteristics would allow for the design of highly functional delivery vehicles for the treatment of many serious human diseases.
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sobczynski
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Phapanin
authors.initials: P
authors.lastname: Charoenphol
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heslinga
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Onyskiw
authors.affiliation: Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Katawut
authors.initials: K
authors.lastname: Namdee
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Omolola
authors.initials: O
authors.lastname: Eniola-Adefeso
mesh_terms: D000327:Adsorption; D001798:Blood Proteins / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D022001:Focal Adhesions; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011485:Protein Binding; D000066970:Protein Corona / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D004337:Drug Carriers; D000066970:Protein Corona; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid