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Oppositely-charged polymers can undergo an associative phase separation process known as complex coacervation, which is driven by the electrostatic attraction between the two polymer species. This driving force for phase separation can be harnessed to drive self-assembly, via pairs of block copolyelectrolytes with opposite charge and thus favorable coulombic interactions. There are few predictions of coacervate self-assembly phase behavior due to the wide variety of molecular and environmental parameters, along with fundamental theoretical challenges. In this paper, we use recent advances in coacervate theory to predict the solution-phase assembly of diblock polyelectrolyte pairs for a number of molecular design parameters (charged block fraction, polymer length). Phase diagrams show that self-assembly occurs at high polymer, low salt concentrations for a range of charge block fractions. We show that we qualitatively obtain limiting results seen in the experimental literature, including the emergence of a high polymer-fraction reentrant transition that gives rise to a self-compatibilized homopolymer coacervate behavior at the limit of high charge block fraction. In intermediate charge block fractions, we draw an analogy between the role of salt concentration in coacervation-driven assembly and the role of temperature in χ -driven assembly. We also explore salt partitioning between microphase separated domains in block copolyelectrolytes, with parallels to homopolyelectrolyte coacervation.
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This content will become publicly available on October 1, 2026
Exploring the effects of excipients on complex coacervation
Complex coacervation is an associative liquid–liquid phase separation phenomenon that takes place due to the electrostatic complexation of oppositely-charged polyelectrolytes and the entropic gains associated with the release of bound counterions and rearrangement of solvent. The aqueous nature of coacervation has resulted in its broad use in systems requiring high biocompatibility. The significance of electrostatic interactions in coacervates has meant that studies investigating the phase behaviors of these systems have tended to focus on parameters such as the charge stoichiometry of the polyions, the solution pH, and the ionic strength. However, the equilibrium that exists between the polymer-rich coacervate phase and the polymer-poor supernatant phase represents a balance among attractive electrostatic interactions and excluded volume repulsions as well as osmotic pressure effects. As such, we hypothesize that it should be possible to tune coacervate phase behavior via the addition of non-electrostatic excipients which would partition between the two phases and potentially alter both the solvent quality and the osmotic pressure balance. In particular, our work focuses on small molecule excipients such as sugars, amino acids, and other additives that have a history of use in vaccine formulation. We quantified the ability of these excipients to partition into the coacervate phase, and their potential for destabilizing the phase separation. Furthermore, we demonstrate that these additives can be combined with complex coacervation in the context of a virus formulation.
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- Award ID(s):
- 2118788
- PAR ID:
- 10589542
- Publisher / Repository:
- Journal of Colloid and Interface Science
- Date Published:
- Journal Name:
- Journal of Colloid and Interface Science
- Volume:
- 695
- Issue:
- C
- ISSN:
- 0021-9797
- Page Range / eLocation ID:
- 137808
- Subject(s) / Keyword(s):
- Complex coacervation Excipient Encapsulation Virus Solvent quality
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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