Silica Colloidal Crystals as Emerging Materials for High-Throughput Protein Electrophoresis

Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 4

Abstract

Silica colloidal crystals are a new type of media for protein electrophoresis, and they are assessed for their promise in rapidly measuring aggregation of monoclonal antibodies. The nature of silica colloidal crystals is described in the context of the need for a high-throughput separation tool for optimizing the formulations of protein drugs for minimal aggregation. The fundamental relations between molecular weight and mobility in electrophoresis are used to make a theoretical comparison of selectivity between gels and colloidal crystals. The results show that the selectivity is similar for these media, but slightly higher, 10%, for gels, and the velocity is inherently lower than that for gels due to the smaller free volume fraction. These factors are more than compensated for by lower broadening in colloidal crystals. These new media give plate heights of only 0.15 μm for the antibody monomer and 0.42 μm for the antibody dimer. The monoclonal antibody is separated from its dimer in 72 s over a distance of only 6.5 mm. This is five times faster than size-exclusion chromatography, with more than tenfold miniaturization, and amenable to parallel separations, all of which are promising for the design of high-throughput devices for optimizing protein drug formulations.

Authors and Affiliations

Nadine K. Njoya, Robert E. Birdsall, Mary J. Wirth

Keywords

Related Articles

Time-and concentration-dependent penetration of doxorubicin in prostate tumors

The penetration of paclitaxel into multilayered solid tumors is time- and concentration-dependent, a result of the drug-induced apoptosis and changes in tissue composition. This study evaluates whether this tissue penetr...

Repeat Analysis and Incurred Sample Reanalysis: Recommendation for Best Practices and Harmonization from the Global Bioanalysis Consortium Harmonization Team

The A7 harmonization team (A7 HT), a part of the Global Bioanalysis Consortium (GBC), focused on reviewing best practices for repeat analysis and incurred sample reanalysis (ISR) as applied during regulated bioanalysis....

A Multi-Tiered Analytical Approach For the Analysis and Quantitation of High-Molecular-Weight Aggregates in a Recombinant Therapeutic Glycoprotein

In this study, we have investigated sedimentation velocity ultracentrifugation (AUC-SV), size exclusion chromatography (SEC), and circular dichroism (CD) methods for the detection and quantitation of protein aggregates u...

Model system to study classical nuclear export signals

Signal-mediated protein transport through the nuclear pore complex is of considerable interest in the field of molecular pharmaceutics. Nuclear localization signals can be used to target genes/antisense delivery systems...

Neuropeptide-processing enzymes: Applications for drug discovery

Neuropeptides serve many important roles in communication between cells and are an attractive target for drug discovery. Neuropeptides are produced from precursor proteins by selective cleavages at specific sites, and ar...

Download PDF file
  • EP ID EP681161
  • DOI  10.1208/s12248-013-9506-2
  • Views 83
  • Downloads 0

How To Cite

Nadine K. Njoya, Robert E. Birdsall, Mary J. Wirth (2013). Silica Colloidal Crystals as Emerging Materials for High-Throughput Protein Electrophoresis. The AAPS Journal, 15(4), -. https://europub.co.uk/articles/-A-681161