Investigation of the Protein Corona on Polyvinyl Alcohol-Stabilized Polymeric Nanoparticles

Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) are widely used for targeted drug delivery in oncology. Upon intravenous administration, these particles are coated by biomolecules, forming protein corona that determines biodistribution of nanoparticles. While polyvinyl alcohol (PVA) is commonly used in particle formulation, its influence on the corona remains poorly understood. In this study, we determined the impact of residual PVA concentration on the protein corona composition of polymeric nanoparticles.

In this work, paclitaxel-loaded PLGA nanoparticles were prepared with varying PVA concentrations: 0.5% (NP1), 1% (NP2), 2% (NP3) and 5% (NP4). Characterization showed that increasing PVA concentration resulted in smaller particle size and lower polydispersity: NP1 (247±1 nm, PDI 0.305±0.009), NP2 (180±1 nm, PDI 0.109±0.015), NP3 (171±1 nm, PDI 0.057±0.015), and NP4 (177±2 nm, PDI 0.063±0.025). All formulations exhibited negative ζ-potential (ranging from -15.4±0.6 to -11.2±0.5 mV).

To form protein corona, particles were incubated with fetal bovine serum as a model source of proteins. Adsorbed proteins were quantified using the bicinchoninic acid assay. Increasing PVA concentration correlated with a decrease in adsorbed proteins, with NP1 showing the highest protein concentration (163±21 µg/µg particles) and NP4 the lowest (6±2 µg/µg particles). The qualitative corona composition was analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). LC-MS/MS revealed 393 proteins of different identities in all examined particles. A Venn diagram revealed a core set of common proteins across samples, but NP4 contained the highest number of unique proteins, indicating that high PVA content alters corona composition.

These results demonstrate that residual PVA concentration significantly affects both quantitative and qualitative protein corona composition. This study provides a rational basis for optimizing nanoparticle formulations to control corona formation. Further studies are needed to determine whether these differences can be exploited to improve tumor targeting and reduce off-target accumulation, thereby enhancing the therapeutic efficacy of encapsulated anticancer drugs.