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Issue 6, 2013
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Tunable equilibrium nanocluster dispersions at high protein concentrations

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Abstract

Solutions of therapeutic proteins often gel and become too viscous to deliver via subcutaneous injection at high protein concentrations (>200 mg ml−1). Herein, we demonstrate that protein molecules can be crowded into colloidally stable dispersions of distinct nanoclusters that exhibit equilibrium hydrodynamic diameters without gelation at very high concentrations (up to 320 mg ml−1). The nanoclusters form spontaneously upon concentration of protein solutions in the presence of a crowding agent, for example trehalose. Remarkably nanoclusters of the same size are produced by dilution of protein powder in buffer. Nanocluster size is stable for extended time periods, and upon frozen storage and thawing. Thus, the nanocluster diameter appears to be governed by equilibrium behavior arising from a balance of short and long-ranged monomer–monomer, monomer–cluster and cluster–cluster interactions, as calculated by a free energy model.

Graphical abstract: Tunable equilibrium nanocluster dispersions at high protein concentrations

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Article information


Submitted
27 Oct 2012
Accepted
12 Dec 2012
First published
21 Dec 2012

Soft Matter, 2013,9, 1766-1771
Article type
Communication

Tunable equilibrium nanocluster dispersions at high protein concentrations

A. U. Borwankar, A. K. Dinin, J. R. Laber, A. Twu, B. K. Wilson, J. A. Maynard, T. M. Truskett and K. P. Johnston, Soft Matter, 2013, 9, 1766
DOI: 10.1039/C2SM27480A

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