Biodegradable "Smart" Polyphosphazenes with Intrinsic Multifunctionality as Intracellular Protein Delivery Vehicles

Biomacromolecules
Andre P MartinezAlexander K Andrianov

Abstract

A series of biodegradable drug delivery polymers with intrinsic multifunctionality have been designed and synthesized utilizing a polyphosphazene macromolecular engineering approach. Novel water-soluble polymers, which contain carboxylic acid and pyrrolidone moieties attached to an inorganic phosphorus-nitrogen backbone, were characterized by a suite of physicochemical methods to confirm their structure, composition, and molecular sizes. All synthesized polyphosphazenes displayed composition-dependent hydrolytic degradability in aqueous solutions at neutral pH. Their formulations were stable at lower temperatures, potentially indicating adequate shelf life, but were characterized by accelerated degradation kinetics at elevated temperatures, including 37 °C. It was found that synthesized polyphosphazenes are capable of environmentally triggered self-assembly to produce nanoparticles with narrow polydispersity in the size range of 150-700 nm. Protein loading capacity of copolymers has been validated via their ability to noncovalently bind avidin without altering biological functionality. Acid-induced membrane-disruptive activity of polyphosphazenes has been established with an onset corresponding to the endosomal pH range and bei...Continue Reading

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Citations

Sep 22, 2018·Advanced Healthcare Materials·Liang ChengZhiyuan Zhong
Feb 7, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Zhipeng NiLison Teng
Jan 22, 2019·Artificial Cells, Nanomedicine, and Biotechnology·Hamed NosratiHamidreza Kheiri Manjili
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Dec 8, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Alexander K Andrianov, Robert Langer
Feb 14, 2021·Pharmaceutics·Bareera QamarSilvia Muro
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Mar 24, 2018·Industrial & Engineering Chemistry Research·Anne LinhardtIan Teasdale
Oct 3, 2020·Chemistry of Materials : a Publication of the American Chemical Society·Johoon KimDavid P Cormode

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