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.