Comparative whole corona fingerprinting and protein adsorption thermodynamics of PLGA and PCL nanoparticles in human serum

Abstract

Nanoparticles (NPs) based on biocompatible and biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) represent effective systems for systemic drug delivery. Upon injection into the blood circuit, the NP surface is rapidly modified due to adsorption of proteins that form a ‘protein corona’ (PC). The PC plays an important role in cellular targeting, uptake and NP bio-distribution. Hence, the study of interactions between NPs and serum proteins appears as key for biomedical applications and safety of NPs. In the present work, we report on the comparative protein fluorescence quenching extent, thermodynamics of protein binding and identification of proteins in the soft and hard corona layers of PLGA and PCL NPs. NPs were prepared via a single emulsion-solvent evaporation technique and characterized with respect to size, zeta potential, surface morphology and hydrophobicity. Protein fluorescence quenching experiments were performed against human serum albumin. The thermodynamics of serum protein binding onto the NPs was studied using isothermal titration calorimetry. Semi-quantitative analysis of proteins in the PC layers was conducted using gel electrophoresis and mass spectrometry using human serum.