Protein Stabilization in Aqueous Solutions of Polyphosphazene Polyelectrolyte and Non-Ionic Surfactants

Abstract

Applications of polyelectrolytes as pharmaceutical excipients or biologically active agents generated an increased interest in formulations, in which ionic macromolecules share the same milieu with protein drugs or vaccine antigens. Macromolecular interactions, which often take place in such systems, can potentially impact formulation activity and stability. The present article reports that poly[di(carboxylatophenoxy)phosphazene], disodium salt (PCPP), which has been previously shown to be a potent vaccine adjuvant, also displays a strong protein stabilizing effect in aqueous solutions that can be significantly amplified in the presence of nonionic surfactants. The phenomenon is studied in the context of macromolecular interactions in the system and is linked to the formation of PCPP-protein and PCPP-protein-surfactant complexes.

The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells

“…Although more studies need to be conducted to investigate functional stability of the antigen in the formulations, the results clearly show that the addition of PCPP and the formation of macromolecular complexes with Gag alleviate undesirable molecular changes thereby promoting antigen stability. These results are also in line with previous findings on the protein stabilizing effect of PCPP in aqueous solutions [5,13].…”

“…Instead, polyphosphazenes are thought to engage in noncovalent interactions with antigens to form water-soluble multimeric complexes [11] with resulting in vivo complex activity depending on molecular weight, the amount of antigen bound (protein loading), and the degree of complex compaction (effective antigen presentation). Finally, PCPP can enhance thermal stability of vaccine antigens [5,13], a critical requirement for many successful vaccine formulations [14,15] that may improve vaccine shelf life and reduce dependence of their distribution and storage on cold-chain facilities [16,17].…”

Enhanced thermal stability and pH behavior of glucose oxidase on electrostatic interaction with polyethylenimine

“…Among these polymers, polyelectrolytes have been frequently selected to trap and immobilize several important enzymes [8,9]. In this regard, increasing interest has been observed in the use of polyelectrolytes as an excipient in the pharmaceutical industry and as a part of the formulation of biologically active agents such as proteins [10].…”

Like-charged protein-polyelectrolyte complexation driven by charge patches

“…5 Another example is that PEs are also employed to stabilize or destabilize proteins in solution. 6,7 The interaction between proteins and PEs depends on several chemical and physical factors, i.e., the pH, ionic strength, protein surface charge distributions, and the PE charge, length, and stiffness. 8,9 As a consequence, protein-PE complexation is a highly intricate process with a large variety of resulting stable structures.…”