Influence of surface charge density on protein adsorption on polymeric nanoparticles: analysis by two-dimensional electrophoresis.

Plasma protein adsorption is regarded as a key factor for the in vivo organ distribution of intravenously administered colloidal drug carriers, and strongly depends on their surface characteristics, e.g. surface hydrophobicity or charge. A range of polymeric nanoparticles with a steep variation of the surface charge density was synthesized as model drug carriers. Physicochemical parameters, i.e. particle size, surface charge density, hydrophobicity and surface topography were determined. Two-dimensional electrophoresis (2-DE) was employed for determination of particle interactions with human plasma proteins. Increasing surface charge density showed an increase in plasma protein adsorption, but did not show differences in the detected protein species. For the first time it was possible to show plasma protein adsorption patterns on a range of nanoparticles with variation of only one parameter, i.e. the charge, while size and surface hydrophobicity remain practically unchanged. The knowledge about the interactions of proteins with particulate surfaces can be exploited for the future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins (e.g. microparticles and implants).

[1]  Michel Veillard,et al.  Non-stealth (poly(lactic acid/albumin)) and stealth (poly(lactic acid-polyethylene glycol)) nanoparticles as injectable drug carriers , 1995 .

[2]  R. Müller,et al.  The controlled intravenous delivery of drugs using PEG-coated sterically stabilized nanospheres. , 1995, Advanced drug delivery reviews.

[3]  W. Norde,et al.  Why proteins prefer interfaces. , 1991, Journal of biomaterials science. Polymer edition.

[4]  H. Ayhan,et al.  Phagocytosis of monosize polystyrene-based microspheres having different size and surface properties. , 1995, Journal of biomaterials science. Polymer edition.

[5]  D. Hochstrasser,et al.  Colloidal carriers for intravenous drug targeting: Plasma protein adsorption patterns on surface‐modified latex particles evaluated by two‐dimensional polyacrylamide gel electrophoresis , 1993, Electrophoresis.

[6]  R. Müller,et al.  Analysis of plasma protein adsorption onto polystyrene particles by two‐dimensional electrophoresis: Comparison of sample application and isoelectric focusing techniques , 2000, Electrophoresis.

[7]  F. .. Nieves,et al.  Effect of electrolyte type on the electrokinetic behavior of sulfonated polystyrene model colloids , 1993 .

[8]  H M Patel,et al.  Serum opsonins and liposomes: their interaction and opsonophagocytosis. , 1992, Critical reviews in therapeutic drug carrier systems.

[9]  W. Norde,et al.  Effect of the Nature of the Substrate on the Adsorption of Human Plasma Albumin , 1982 .

[10]  L. Sherman,et al.  Specific binding of soluble fibrin to macrophages , 1977, The Journal of experimental medicine.

[11]  R. Müller,et al.  Nanoparticles with decreasing surface hydrophobicities: influence on plasma protein adsorption. , 2000, International journal of pharmaceutics.

[12]  A. Caprani,et al.  Influence of surface charge on adsorption of fibrinogen and/or albumin on a rotating disc electrode of platinum and carbon. , 1990, Biomaterials.

[13]  B. Paulke,et al.  Electrophoretic 3D-Mobility Profiles of Latex Particles with Different Surface Groups , 1995 .

[14]  D. B. Zilversmit,et al.  The effect of particle size on blood clearance and tissue distribution of radioactive gold colloids. , 1952, The Journal of laboratory and clinical medicine.

[15]  T. Allen,et al.  Long-circulating, polyethylene glycol-grafted immunoliposomes , 1996 .

[16]  M. Woodle,et al.  Controlling liposome blood clearance by surface-grafted polymers. , 1998, Advanced drug delivery reviews.

[17]  R. Müller,et al.  Identification of plasma proteins facilitated by enrichment on particulate surfaces: Analysis by two‐dimensional electrophoresis and N‐terminal microsequencing , 1997, Electrophoresis.

[18]  D. Wilkins,et al.  Studies on the relationship between the electrophoretic properties of colloids and their blood clearance and organ distribution in the rat. , 1966, British journal of experimental pathology.

[19]  C. J. Oss,et al.  Phagocytosis as a Surface Phenomenon , 1978 .

[20]  Y Ikada,et al.  Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. , 1988, Biomaterials.

[21]  G. Gregoriadis,et al.  Tissue distribution of liposomes exhibiting long half-lives in the circulation after intravenous injection. , 1985, Biochimica et biophysica acta.

[22]  R. Kapur,et al.  Field-dependent fibroblast orientation on charged surfaces is independent of polarity and adsorbed serum proteins. , 1993, Biomaterials.

[23]  C. Merril,et al.  Simplified silver protein detection and image enhancement methods in polyacrylamide gels , 1982 .

[24]  R. Schwendener,et al.  The effects of charge and size on the interaction of unilamellar liposomes with macrophages. , 1984, Biochimica et biophysica acta.

[25]  P. Mannucci,et al.  Binding of fibrinogen to human monocytes. , 1986, The Journal of clinical investigation.

[26]  Amos Bairoch,et al.  Plasma and red blood cell protein maps: Update 1993 , 1993, Electrophoresis.

[27]  W. Norde,et al.  The adsorption of HPA and Bovine Pancreas Ribonuclease at Negatively Charged Polystyrene Latices. V. Microcalorimetry , 1978 .

[28]  V. Neuhoff,et al.  Visualization of proteins with a silver “stain”: A critical analysis , 1981 .

[29]  M. Lück,et al.  Analysis of plasma protein adsorption on polymeric nanoparticles with different surface characteristics. , 1998, Journal of biomedical materials research.

[30]  W. Norde,et al.  The adsorption of HPA and Bovine Pancreas Ribonuclease at Negatively Charged Polystyrene Latices. II. Hydrogen-Ion Titrations , 1978 .

[31]  D. Hochstrasser,et al.  A nonlinear wide‐range immobilized pH gradient for two‐dimensional electrophoresis and its definition in a relevant pH scale , 1993, Electrophoresis.

[32]  R. Müller,et al.  Plasma protein adsorption patterns on emulsions for parenteral administration: Establishment of a protocol for two‐dimensional polyacrylamide electrophoresis , 1998, Electrophoresis.

[33]  T. Allen,et al.  Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. , 1989, Biochimica et biophysica acta.