Protein-loaded soluble and nanoparticulate formulations of ionic polyphosphazenes and their interactions on molecular and cellular levels.

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TitleProtein-loaded soluble and nanoparticulate formulations of ionic polyphosphazenes and their interactions on molecular and cellular levels.
Publication TypeJournal Article
Year of Publication2020
AuthorsAndrianov, AK, Marin, A, Deng, J, Fuerst, TR
JournalMater Sci Eng C Mater Biol Appl
Volume106
Pagination110179
Date Published2020 Jan
ISSN1873-0191
Abstract

Nanoparticulate and water-soluble formulations of ionic polyphosphazenes and protein cargo - lysozyme (LYZ) were prepared by their self-assembly in aqueous solutions at near physiological pH (pH 7.4) in the presence and absence of an ionic cross-linker - spermine tetrahydrochloride. Efficiency of LYZ encapsulation, physico-chemical characteristics of formulations, and the effect of reaction parameters were investigated using asymmetric flow field flow fractionation (AF4) and dynamic light scattering (DLS) methods. The effect of both polymer formulations on encapsulated LYZ was evaluated using soluble oligosaccharide substrate, whereas their ability to present the protein to cellular surfaces was assessed by measuring enzymatic activity of encapsulated LYZ against Micrococcus lysodeikticus cells. It was found that both soluble and cross-linked polymer matrices reduce lysis of bacterial cells by LYZ, whereas activity of encapsulated protein against oligosaccharide substrate remained practically unchanged indicating no adverse effect of polyphosphazene on protein integrity. Moreover, nanoparticulate formulations display distinctly different behavior in cellular assays when compared to their soluble counterparts. LYZ encapsulated in polyphosphazene nanoparticles shows approximately 2.5-fold higher activity in its ability to lyse cells as compared with water-soluble LYZ-PCPP formulations. A new approach to PEGylation of polyphosphazene nanoparticles was also developed. The method utilizes a new ionic polyphosphazene derivative, which contains graft (polyethylene glycol) chains. PEGylation allows for an improved control over the size of nanoparticles and broader modulation of their cross-linking density, while still permitting for protein presentation to cellular substrates.

DOI10.1016/j.msec.2019.110179
Alternate JournalMater Sci Eng C Mater Biol Appl
PubMed ID31753403
PubMed Central IDPMC6903416
Grant ListR01 AI132213 / AI / NIAID NIH HHS / United States
R01 CA227142 / CA / NCI NIH HHS / United States