title: Impact of poly(lactic-co-glycolic acid) nanoparticle surface charge on protein, cellular and haematological interactions.
abstract: 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.
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India.
authors.forename: Gopikrishna J
authors.initials: GJ
authors.lastname: Pillai
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India.
authors.forename: M M
authors.initials: MM
authors.lastname: Greeshma
authors.affiliation: Amrita Centre for Nanosciences and Molecular Medicine, Amrita Vishwa Vidyapeetham, Kochi, 682041 Kerala, India. Electronic address: deepthymenon@aims.amrita.edu.
authors.forename: Deepthy
authors.initials: D
authors.lastname: Menon
mesh_terms: D001777:Blood Coagulation; D006461:Hemolysis; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D011506:Proteins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: Cell uptake; Cell-nanoparticle interactions; Haematological interactions; PLGA nanoparticles; Protein binding; Surface charge