title: Biodegradable nanoparticles mimicking platelet binding as a targeted and controlled drug delivery system.
abstract: This research aims to develop targeted nanoparticles as drug carriers to the injured arterial wall under fluid shear stress by mimicking the natural binding ability of platelets via interactions of glycoprotein Ib-alpha (GPIbα) of platelets with P-selectin of damaged endothelial cells (ECs) and/or with von Willebrand factor (vWF) of the subendothelium. Drug-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles were formulated using a standard emulsion method and conjugated with glycocalicin, the external fraction of platelet GPIbα, via carbodiimide chemistry. Surface-coated and cellular uptake studies in ECs showed that conjugation of PLGA nanoparticles, with GPIb, significantly increased nanoparticle adhesion to P-selectin- and vWF-coated surfaces as well as nanoparticle uptake by activated ECs under fluid shear stresses. In addition, effects of nanoparticle size and shear stress on adhesion efficiency were characterized through parallel flow chamber studies. The observed decrease in bound nanoparticle density with increased particle sizes and shear stresses is also explained through a computational model. Our results demonstrate that the GPIb-conjugated PLGA nanoparticles can be used as a targeted and controlled drug delivery system under flow conditions at the site of vascular injury.
authors.affiliation: Department of Bioengineering, University of Texas at Arlington, TX, United States.
authors.forename: Soujanya
authors.initials: S
authors.lastname: Kona
authors.forename: Jing-Fei
authors.initials: JF
authors.lastname: Dong
authors.forename: Yaling
authors.initials: Y
authors.lastname: Liu
authors.forename: Jifu
authors.initials: J
authors.lastname: Tan
authors.forename: Kytai T
authors.initials: KT
authors.lastname: Nguyen
mesh_terms: D000268:Adhesiveness; D000818:Animals; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D008954:Models, Biological; D053758:Nanoparticles; D036103:Nanotechnology; D019007:P-Selectin / Q000378:metabolism; D010316:Particle Size; D010973:Platelet Adhesiveness; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013314:Stress, Mechanical; D013678:Technology, Pharmaceutical / Q000379:methods; D057772:Vascular System Injuries / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007166:Immunosuppressive Agents; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; C023592:glycocalicin; D014841:von Willebrand Factor; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone