Direct visualization of protein adsorption to primary containers by gold nanoparticles.

Adsorption of proteins to primary containers can result in protein loss, protein denaturation, or aggregation. We report a simple and effective method to directly detect and visualize adsorption of proteins to container surfaces by staining adsorbed proteins with gold nanoparticles, which bind proteins nonspecifically. The gold nanoparticle staining method was applied to study adsorption to siliconized glass prefilled syringes (PFSs) of a therapeutic protein in a liquid formulation. The protein was found to preferentially adsorb to glass surfaces over siliconized surfaces in PFSs. The presence of adsorbed proteins on glass surfaces was confirmed by in situ Raman spectroscopy. Gold nanoparticle staining patterns revealed that adsorption of proteins to hydrophobic cyclic olefin polymer plastic vials was minimized compared with hydrophilic type I glass vials. Bovine serum albumin (BSA) also preferentially adsorbed to glass surfaces compared with siliconized surfaces as revealed by the gold staining patterns in PFS incubated with BSA, supporting the use of albumin to minimize loss of proteins in glass containers. The method is particularly valuable for high-concentration protein formulations in which adsorption of proteins to containers cannot be easily detected by other methods.

[1]  Joey Pollastrini,et al.  Tungsten-induced protein aggregation: solution behavior. , 2009, Journal of pharmaceutical sciences.

[2]  Theodore W Randolph,et al.  Precipitation of a monoclonal antibody by soluble tungsten. , 2009, Journal of pharmaceutical sciences.

[3]  Theodore W Randolph,et al.  Silicone oil- and agitation-induced aggregation of a monoclonal antibody in aqueous solution. , 2009, Journal of pharmaceutical sciences.

[4]  A. Yu,et al.  Investigation on the interaction between colloidal gold and human complement factor 4 at different pH by spectral methods. , 2006, Colloids and surfaces. B, Biointerfaces.

[5]  C. R. Middaugh,et al.  Silicone oil induced aggregation of proteins. , 2005, Journal of pharmaceutical sciences.

[6]  S. Chah,et al.  Gold nanoparticles as a colorimetric sensor for protein conformational changes. , 2005, Chemistry & biology.

[7]  M. Manning,et al.  Heterogeneous nucleation-controlled particulate formation of recombinant human platelet-activating factor acetylhydrolase in pharmaceutical formulation. , 2005, Journal of pharmaceutical sciences.

[8]  Georges Belfort,et al.  Protein structural perturbation and aggregation on homogeneous surfaces. , 2005, Biophysical journal.

[9]  Jeffrey J. Gray,et al.  The interaction of proteins with solid surfaces. , 2004, Current opinion in structural biology.

[10]  L. Schlapbach,et al.  Study of adsorption and viscoelastic properties of proteins with a quartz crystal microbalance by measuring the oscillation amplitude. , 2003, Journal of colloid and interface science.

[11]  S. S. Qadry,et al.  Evaluation of CZ-resin vials for packaging protein-based parenteral formulations. , 2003, International journal of pharmaceutics.

[12]  V. Vasudevan,et al.  Formulation development of protein dosage forms. , 2002, Pharmaceutical biotechnology.

[13]  Jeong‐Yeol Yoon,et al.  PROTEIN ADSORPTION ON POLYMER PARTICLES , 2002 .

[14]  D. Grier,et al.  The charge of glass and silica surfaces , 2001, cond-mat/0105149.

[15]  W. Norde,et al.  BSA structural changes during homomolecular exchange between the adsorbed and the dissolved states. , 2000, Journal of biotechnology.

[16]  S. Tzannis,et al.  Irreversible inactivation of interleukin 2 in a pump-based delivery environment. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Duncan,et al.  Influence of surfactants upon protein/peptide adsorption to glass and polypropylene , 1995 .

[18]  M. Natan,et al.  Self-Assembled Metal Colloid Monolayers: An Approach to SERS Substrates , 1995, Science.

[19]  C. Gao,et al.  The dynamic analysis of stick-slip motion , 1994 .

[20]  D. Volkin,et al.  The adsorption of proteins to pharmaceutical container surfaces , 1992 .

[21]  A. Lenhoff,et al.  TIRF of salt and surface effects on protein adsorption , 1992 .

[22]  P. Courtoy,et al.  A model of protein-colloidal gold interactions. , 1987, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[23]  I. Lundström,et al.  Immunoglobulin G and secretory fibronectin adsorption to silica: The influence of conformational changes on the surface , 1987 .

[24]  D. Holden,et al.  Protein blotting: detection of proteins with colloidal gold, and of glycoproteins and lectins with biotin-conjugated and enzyme probes. , 1985, Analytical biochemistry.

[25]  R. Eckel,et al.  Quantification of cell death in human fibroblasts by measuring the loss of [14C]thymidine from prelabeled cell monolayers. , 1981, Analytical biochemistry.

[26]  T. Mizutani.  Estimation of protein and drug adsorption onto silicone-coated glass surfaces. , 1981, Journal of pharmaceutical sciences.

[27]  T. Mizutani,et al.  Estimation of adsorption of drugs and proteins on glass surfaces with controlled pore glass as a reference. , 1978, Journal of pharmaceutical sciences.

[28]  R. Messing.  ADSORPTION OF PROTEINS ON GLASS SURFACES AND PERTINENT PARAMETERS FOR THE IMMOBILIZATION OF ENZYMES IN THE PORES OF INORGANIC CARRIERS , 1975 .