Harvard School of Engineering and Applied Sciences, 29 Oxford Street, Cambridge, Massachussets 02138, USA.
Biomacromolecules. 2010 Jul 12;11(7):1863-72. doi: 10.1021/bm100384z.
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.
为了延长气溶胶递送的生长因子在肺部中的滞留时间，以促进干细胞归巢/激活，我们研究了将血管内皮生长因子（VEGF）与葡聚糖硫酸酯（DS）和壳聚糖（CS）聚电解质复合的制剂。在 VEGF/DS/CS 比为 0.12:1:0.33 时，发现 VEGF 的最佳掺入量，这导致纳米颗粒复合物的直径为 612+/-79nm，且 ζ 电位为-31+/-1mV。该复合物在生理溶液中塌陷，并在体外以两相时程释放 VEGF。然而，在大鼠肺部中，以复合物形式递送的 VEGF 以恒定的指数衰减率被清除，比以游离形式递送的速度慢 8 倍。这种延长的 VEGF 保留可能是由于 VEGF 与 DS 和内源性糖胺聚糖的平衡结合所致。当与这些糖结合时，其他与糖胺聚糖结合的蛋白质（包括许多生长因子）预计也会产生类似的保留效果。由于其独特的应用，这种类型的复合物或许可以更好地描述为纳米糖复合物。
