Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates

摘要: Biodegradable polymeric nanoparticles are widely recognized as efficacious drug delivery vehicles, yet the rational engineering of nanoparticle surfaces in order to improve biodistribution, reduce clearance, and/or targeting remains a significant challenge. We have previously demonstrated that an amphiphilic conjugate avidin and palmitic acid can be used modify poly(lactic-co-glycolic acid) (PLGA) particle display functional groups, allowing for facile attachment biotinylated ligands or steric stabilization. Here, we hypothesized incorporation, density, stability surface-presented could modulated through varying lipophilicity its fatty partner. tested this hypothesis by generating set novel conjugates incorporating common acids. found conjugation linoleic resulted ~60% increase incorporation on surface compared avidin-palmitic acid, which exhibited highest previous studies. Further, acid-avidin yielded with enhanced ability bind method; modified avidin-linoleic bound ~170% more biotin-HRP than those made ~1300% particles without conjugated avidin. Most critically, increased ligand density anti-CD4-targeted formulated 5% binding CD4(+) T cells. Thus conclude facilitates PLGA nanoparticles, resulting enhancement cellular targeting.