Are stabilizers, located on the surface of PLGA nanoparticles, able to modify the protein adsorption pattern?

Poly(lactic-co-glycolic acid) (PLGA) is an FDA-approved, biodegradable, and biocompatible polymer, which makes it a promising starting material for the development of nanoparticles. However, in vivo studies have revealed a short biological half-life due to recognition and consequently internalization of these nanoparticles by cells of the mononuclear phagocyte system, resulting in their accumulation in the liver and spleen. In this study, we analyzed the adsorption pattern of proteins on PLGA nanoparticles after incubation with human plasma and human serum. For this analysis, different nanoparticle stabilizer systems were manufactured, and the adsorbed protein amounts were determined after incubation. Additionally, the adsorbed proteins were identified and enrichment and depletion processes of specific proteins that take place during protein incubation were measured via LC-MS/MS. The results showed a high enrichment of several opsonins on the nanoparticle surface and a depletion of most dysopsonins. Therefore, we hypothesize that an explanation for the unfavorable in vivo behavior of PLGA nanoparticles could be the formation of a biomolecular corona with a preferential adsorption of opsonins. Furthermore, we aimed to analyze whether different stabilizers, located on the surface of PLGA nanoparticles, were able to modify the protein adsorption pattern. Our findings suggest that the use of different stabilizers can influence the amount of total bound proteins on the nanoparticle surface. However, the change of stabilizers has only a minor impact on the composition of the biomolecular corona.