Effect of nanoparticle size and PEGylation on the protein corona of PLGA nanoparticles
| Autor: | Klaus Langer, Fabian C. Herrmann, Nora C. Stein, Hans-Ulrich Humpf, Katrin Partikel, Robin Korte, Dennis Mulac |
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| Rok vydání: | 2019 |
| Předmět: |
Surface Properties
Polyesters Pharmaceutical Science Nanoparticle Protein Corona 02 engineering and technology 030226 pharmacology & pharmacy Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems 0302 clinical medicine Polylactic Acid-Polyglycolic Acid Copolymer Humans Particle Size Bradford protein assay Polyacrylamide gel electrophoresis Drug Carriers Chromatography technology industry and agriculture General Medicine 021001 nanoscience & nanotechnology Biodegradable polymer PLGA chemistry PEGylation Nanoparticles Adsorption 0210 nano-technology Polyglycolic Acid Biotechnology Protein adsorption |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 141:70-80 |
| ISSN: | 0939-6411 |
| Popis: | Upon intravenous administration of nanoparticles (NP) into the bloodstream, proteins bind rapidly on their surface resulting in a formation of a so-called ‘Protein Corona’. These proteins are strongly attached to the NP surface and provide a new biological identity which is crucial for the reaction at the nano-biointerface. The structure and composition of the protein corona is greatly determined by the physico-chemical properties of the NP and the characteristics of the biological environment. The overall objective of this study was to characterize the role of NP size/surface curvature and PEGylation on the formation of the protein corona. Therefore, we prepared NP in a size of 100 and 200 nm using the biodegradable polymers poly(DL-lactide-co-glycolide) (PLGA) and poly(DL-lactide-co-glycolide)-co-polyethylene glycol diblock (PLGA-PEG) and subsequently incubated them with fetal bovine serum (FBS) to induce the formation of a protein corona. After removal of unbound protein, we employed different analytical approaches to study the corona in detail. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) was performed to gain a first impression about amount and composition of the corona proteins. Identification was carried out after tryptic in-solution digestion and liquid chromatography–mass spectrometry/mass spectrometry (LC–MS/MS). In addition, we successfully established the Bradford protein assay as a suitable colorimetric method to quantify total adsorbed protein amount after alkaline hydrolysis of PLGA based NP. Our results revealed that protein adsorption on PLGA- and PLGA-PEG-NP didn’t depend on NP size within the range of 100 and 200 nm. PEGylation led to a significant reduced amount of bound proteins. The depletion of proteins which are involved in immune response was remarkable and indicated a prolonged circulation time in body. |
| Databáze: | OpenAIRE |
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