Net anionic poly(β-amino ester)s: synthesis, pH-dependent behavior, and complexation with cationic cargo.

Autor: Kuenen MK; Department of Chemical Engineering, University of Virginia, Charlottesville, VA, 22903, USA., Cuomo AM; Department of Chemical Engineering, University of Virginia, Charlottesville, VA, 22903, USA., Gray VP; Department of Chemical Engineering, University of Virginia, Charlottesville, VA, 22903, USA., Letteri RA; Department of Chemical Engineering, University of Virginia, Charlottesville, VA, 22903, USA.
Jazyk: angličtina
Zdroj: Polymer chemistry [Polym Chem] 2023 Jan 28; Vol. 14 (4), pp. 421-431. Date of Electronic Publication: 2022 Dec 21.
DOI: 10.1039/d2py01319c
Abstrakt: As hydrolytically-labile, traditionally-cationic polymers, poly(β-amino ester)s (PBAEs) adeptly complex anionic compounds such as nucleic acids, and release their cargo as the polymer degrades. To engineer fully-degradable polyelectrolyte complexes and delivery vehicles for cationic therapeutics, we sought to invert PBAE net charge to generate net anionic PBAEs. Since PBAEs can carry up to a net charge of +1 per tertiary amine, we synthesized a series of alkyne-functionalized PBAEs that allowed installation of 2 anionic thiol-containing molecules per tertiary amine via a radical thiol-yne reaction. Finding dialysis in aqueous solution to lead to PBAE degradation, we developed a preparative size exclusion chromatography method to remove unreacted thiol from the net anionic PBAEs without triggering hydrolysis. The net anionic PBAEs display non-monotonic solution behavior as a function of pH, being more soluble at pH 4 and 10 than in intermediate pH ranges. Like cationic PBAEs, these net anionic PBAEs degrade in aqueous environments with hydrophobic content-dependent hydrolysis, as determined by 1 H NMR spectroscopy. Further, these net anionic PBAEs form complexes with the cationic peptide (GR) 10 , which disintegrate over time as the polymer hydrolyzes. Together, these studies outline a synthesis and purification route to make previously inaccessible net anionic PBAEs with tunable solution and degradation behavior, allowing for user-determined complexation and release rates and providing opportunities for degradable polyelectrolyte complexes and cationic therapeutic delivery.
Competing Interests: Conflicts of interest There are no conflicts to declare.
Databáze: MEDLINE
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