Hydrolytically Degradable PEGylated Polyelectrolyte Nanocomplexes for Protein Delivery.

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TitleHydrolytically Degradable PEGylated Polyelectrolyte Nanocomplexes for Protein Delivery.
Publication TypeJournal Article
Year of Publication2018
AuthorsAndrianov, AK, Marin, A, Martinez, APaul, Weidman, JL, Fuerst, TR
Date Published2018 Jun 28
Abstract<p>Novel oppositely charged polyphosphazene polyelectrolytes containing grafted poly(ethylene glycol) (PEG) chains were synthesized as modular components for the assembly of biodegradable PEGylated protein delivery vehicles. These macromolecular counterparts containing either carboxylic acid or tertiary amino groups were then formulated at near physiological conditions into supramolecular assemblies of nanoscale level - below 100 nm. Nanocomplexes displayed larger size and reduced polydispersity compared to individual macromolecules, and were stable at electroneutral surface charge as assessed by zeta potential measurements in aqueous solutions suggesting their compact polyelectrolyte complex "core" - hydrophilic PEG "shell" structure. Investigation of PEGylated polyphosphazene nanocomplexes as agents for non-covalent PEGylation of therapeutic protein - L-Asparaginase (L-ASP) in vitro demonstrated their ability to dramatically reduce protein antigenicity, as well as improve its thermal stability and proteolytic resistance. All synthesized polyphosphazenes exhibited composition controlled hydrolytic degradability in aqueous solutions at neutral pH and showed greater stability at lower temperatures, indicating adequate solution shelf life. Overall, novel biodegradable polyphosphazene polyelectrolytes capable of spontaneous self-assembly into PEGylated nanoparticulates in aqueous solutions can potentially enable a simple and effective approach to modifying biologically important properties of therapeutic proteins without the need for their covalent modification.</p>
Alternate JournalBiomacromolecules
PubMed ID29953203