Impact of poly(lactic-co-glycolic acid) nanoparticle surface charge on protein, cellular and haematological interactions

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2015-12, Vol.136, p.1058-1066
• Main Authors: Pillai, Gopikrishna J., Greeshma, M.M., Menon, Deepthy
• Format: Article
• Language: English
• Subjects: Blood Coagulation; Cell uptake; Cell-nanoparticle interactions; Cellular; Charged particles; Charging; Haematological interactions; Hemolysis; Lactic Acid - chemistry; Microscopy, Electron, Scanning; Nanoparticles; PLGA nanoparticles; Polyglycolic Acid - chemistry; Protein adsorption; Protein binding; Proteins; Proteins - chemistry; Surface charge; Surface chemistry; Surface Properties
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2015.10.047

[Display omitted] •Impact of polymeric nanoparticle surface charge on interactions with proteins, cell and hematological system was assessed.•PLGA nanoparticles of positive, near-neutral and negative surface charge were prepared.•Among all particles, positively charged PLGA showed maximum protein binding.•Cellular uptake of positively charged PLGA was highest in presence of serum proteins and protein binding did not affect the toxicity of particles.•Heamatological interactions varied with surface charge only at higher concentrations. The initial interactions of nanoparticles with biomolecules have a great influence on its toxicity, efficacy, biodistribution and clearance. The present work is an attempt to understand the impact of surface charge of polymeric nanoparticles on its plasma protein and cellular interactions. Negative, near-neutral and positively charged poly(lactic-co-glycolic acid) [PLGA] nanoparticles were prepared using casein, poly(vinyl alcohol) and poly(ethylene imine) respectively, as surface stabilizers. A significant temporal variation in the hydrodynamic diameter of PLGA nanoparticles was observed in the presence of plasma proteins, which correlated with the amount of proteins adsorbed to each surface. Positively charged particles displayed the maximum size variation and protein adsorption. Cellular uptake of differentially charged nanoparticles was also concurrent with the quantity of adsorbed proteins, though there was no significant difference in their cytotoxicity. Haematological interactions (haemolysis and plasma coagulation times) of positively charged nanoparticles were considerably different from near-neutral and negative nanoparticles. Collectively, the results point to the interplay between plasma protein adsorption and cellular interactions of PLGA nanoparticles, which is governed by its surface charge, thereby necessitating a rational design of nanoparticles.