Self-assembly of polyphosphazene immunoadjuvant with poly(ethylene oxide) enables advanced nanoscale delivery modalities and regulated pH-dependent cellular membrane activity.

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TitleSelf-assembly of polyphosphazene immunoadjuvant with poly(ethylene oxide) enables advanced nanoscale delivery modalities and regulated pH-dependent cellular membrane activity.
Publication TypeJournal Article
Year of Publication2016
AuthorsAndrianov, AK, Marin, A, Fuerst, TR
JournalHeliyon
Volume2
Issue4
Paginatione00102
Date Published2016 Apr
ISSN2405-8440
Abstract

Water-soluble polyphosphazene polyacids, such as poly[di(carboxylatophenoxy)phosphazene] (PCPP), have been of significant interest due to their unique immunoadjuvant and vaccine delivery properties. We report that PCPP can spontaneously self-assemble into intermolecular complexes with common formulation excipients - polyethers in aqueous solutions at neutral pH through the establishment of hydrogen bonds. The resulting advanced PCPP delivery modalities can range from macromolecular assemblies at the nanoscale level to physically cross-linked hydrogels and the physical state can be modulated through varying polymer ratios and molecular weight of polyether. It has been demonstrated that such macromolecular complexes maintain protein-binding ability - a key characteristics of the delivery system. Importantly, the non-covalent modification of PCPP immunoadjuvant with polyethers introduces pH dependent membrane disruptive activity, which is not characteristic for PCPP itself, and is typically correlated to the ability of macromolecular carrier to facilitate endosomal escape. This can potentially affect the mechanism of immunoadjuvant action displayed by PCPP, afford means for its fine-tuning, as well as provide important insights for understanding the relationship between fundamental physico-chemical characteristics of polyphosphazene immunoadjuvants and their activity in vivo.

DOI10.1016/j.heliyon.2016.e00102
Alternate JournalHeliyon
PubMed ID27441274
PubMed Central IDPMC4946082