title: Nanoglycan complex formulation extends VEGF retention time in the lung.
abstract: To extend the retention time of aerosol-delivered growth factors in the lung for stem cell homing/activation purposes, we examined a formulation of vascular endothelial growth factor (VEGF) complexed to dextran sulfate (DS) and chitosan (CS) polyelectrolytes. Optimal incorporation of VEGF was found at a VEGF/DS/CS ratio of 0.12:1:0.33, which resulted in nanoparticle complexes with diameters of 612+/-79 nm and zeta potentials of -31+/-1 mV. The complexes collapsed in physiological solution, and released VEGF in a biphasic time course in vitro. In rat lungs, however, VEGF delivered in the complex was cleared at a constant exponential decay rate, 8-fold slower than that delivered in free form. The extended VEGF retention was likely due to equilibrium binding of VEGF to DS and to endogenous glycosaminoglycans. A similar retention effect is expected with other glycosaminoglycans-binding proteins (including many growth factors) when complexed with these glycans. Owing to its unique application, this type of complex is, perhaps, better described as a nanoglycan complex.
authors.affiliation: Harvard School of Engineering and Applied Sciences, 29 Oxford Street, Cambridge, Massachussets 02138, USA.
authors.forename: E Hunter
authors.initials: EH
authors.lastname: Lauten
authors.forename: Jarod
authors.initials: J
authors.lastname: VerBerkmoes
authors.forename: Justin
authors.initials: J
authors.lastname: Choi
authors.forename: Richard
authors.initials: R
authors.lastname: Jin
authors.forename: David A
authors.initials: DA
authors.lastname: Edwards
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D048271:Chitosan / Q000737:chemistry / Q000627:therapeutic use; D016264:Dextran Sulfate / Q000737:chemistry / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D008168:Lung / Q000378:metabolism* / Q000502:physiology; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D011134:Polysaccharides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011134:Polysaccharides; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D048271:Chitosan; D016264:Dextran Sulfate