title: Adsorption of plasma proteins on uncoated PLGA nanoparticles.
abstract: The biodistribution of nanoparticles is significantly influenced by their interaction with plasma proteins. In order to optimize and possibly monitor the delivery of drugs bound to nanoparticles across the blood-brain barrier (BBB), the protein adsorption pattern of uncoated poly(lactic-co-glycolic acid) (PLGA) nanoparticles after their incubation in human plasma was studied by mass spectrometry. After washing of the particles with water, the proteins were directly digested on the nanoparticle surface using trypsin and then analyzed by nLC MALDI-TOF/TOF. Up to now, the standard method for investigation into the plasma protein adsorption to the particles was 2D gel electrophoresis (2D-PAGE), in certain cases followed by mass spectrometry. The non-gel-based method proposed in the present study provides novel insights into the protein corona surrounding the nanoparticles. The proteins adsorbed on the PLGA nanoparticles after incubation that gave the best signal in terms of quality (high MASCOT score) in human plasma were apolipoprotein E, vitronectin, histidine-rich glycoprotein and kininogen-1. These proteins also are constituents of HDL.
authors: Institute of Pharmaceutical Technology, Goethe University, Frankfurt, Germany.
authors: Karim
authors: K
authors: Sempf
authors: Tabiwang
authors: T
authors: Arrey
authors: Svetlana
authors: S
authors: Gelperina
authors: Tobias
authors: T
authors: Schorge
authors: Björn
authors: B
authors: Meyer
authors: Michael
authors: M
authors: Karas
authors: Jörg
authors: J
authors: Kreuter
mesh_terms: D000327:Adsorption; D001057:Apolipoproteins E / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D001771:Blood Banks; D001798:Blood Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D030562:Databases, Protein; D004337:Drug Carriers / Q000493:pharmacokinetics; D005240:Feasibility Studies; D006801:Humans; D007704:Kininogens / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008075:Lipoproteins, HDL / Q000737:chemistry; D008832:Microchemistry; D053758:Nanoparticles / Q000737:chemistry*; D010449:Peptide Mapping; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011506:Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013499:Surface Properties; D053719:Tandem Mass Spectrometry; D019096:Vitronectin / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D000099053:Histidine-Rich Glycoprotein
chemical_list: D001057:Apolipoproteins E; D001798:Blood Proteins; D004337:Drug Carriers; D007704:Kininogens; D008075:Lipoproteins, HDL; D011506:Proteins; D019096:Vitronectin; D000099053:Histidine-Rich Glycoprotein; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: 2D-PAGE; HDL; MALDI-TOF/TOF; Mass spectrometry; Plasma proteins; Poly(lactide-co-glycolide) (PLGA) nanoparticles; Trypsin