Effect of protein corona on drug release behavior of PLGA nanoparticles

Poly(lactic-co-glycolide) (PLGA) nanoparticles are highly attractive for drug delivery due to their biocompatibility, biodegradability, and potential for controlled release and targeting. Despite these outstanding properties, challenges remain for clinical translation as nanomedicines. One significant factor to address is highlighting the protein corona structure and its effect on the drug release behavior. Protein corona forms upon contact with the bloodstream and influences the fate of the nanoparticles in the body. Here, we synthesize PLGA nanoparticles by miniemulsion/solvent evaporation technique, followed by the formation of protein corona on their surface using either human plasma or fetal bovine serum (FBS). Analysis by both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and liquid chromatography-mass spectrometry (LC-MS) reveals that dysopsonin proteins, mainly albumin, dominate the protein corona structure, suggesting prolonged blood circulation for the PLGA nanoparticles. As an anticancer drug, doxorubicin is encapsulated into PLGA nanoparticles, and in vitro drug release is performed at pH 7.4. While there is a minimal change in cumulative drug release after protein corona formation, our comprehensive analysis through different kinetic models shows that the protein corona alters the drug release profile of PLGA nanoparticles to a modest extent.