Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 423, Issue 2, Pages 516-524Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2011.11.043
Keywords
Biodegradable nanoparticles; Endothelial cells; Platelets; Glycoprotein Ib; Parallel plate flow system
Categories
Funding
- NIH [HL091232, EB009786]
- NSF [0955214]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0955214, 1113040] Funding Source: National Science Foundation
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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 (GPIb alpha) 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 GPIb alpha, 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. (C) 2011 Elsevier B.V. All rights reserved.
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