|Title||Biodegradable "Smart" Polyphosphazenes with Intrinsic Multi-Functionality as Intracellular Protein Delivery Vehicles.|
|Publication Type||Journal Article|
|Year of Publication||2017|
|Authors||Martinez, AP, Qamar, B, Fuerst, TR, Muro, S, Andrianov, AK|
|Date Published||2017 May 19|
A series of biodegradable drug delivery polymers with intrinsic multifunctionality have been designed and synthesized utilizing polyphosphazene macromolecular engineering approach. Novel water-soluble polymers, which contain carboxylic acid and pyrrolidone moieties attached to inorganic phosphorus-nitrogen backbone, were characterized by a suite of physico-chemical 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 between 150 and 700 nm. Protein loading capacity of copolymers has been validated via their ability to non-covalently bind avidin without altering its biological functionality. Acid induced membrane disruptive activity of polyphosphazenes has been established with an onset corresponding to endosomal pH range and being dependent on polymer composition. The synthesized polyphosphazenes facilitated cell-surface interaction followed by time-dependent, vesicular mediated, and saturable internalization of a model protein cargo into cancer cells, demonstrating potential for intracellular delivery.