Degradable polyelectrolytes are useful materials in a variety of biological applications ranging from biomedical implant coatings and immunostimulants to vehicles for drug and nucleic acid delivery. A significant fraction of these applications rely on polyelectrolytes that perform a specific function, after which they degrade into non-toxic byproducts, thereby preventing bioaccumulation and toxicity. Many known degradable polyelectrolytes contain hydrolytically unstable functionalities in the polymer backbone, including ester, anhydride, acetal, carbonate, amide, phosphate, and siloxy ether functionalities. While natural polyelectrolytes such as collagen and chitosan have garnered substantial interest in various biological applications, new approaches to degradable synthetic polyelectrolytes will continue to furnish well-defined materials with tunable structures, controlled molecular weights, and variable backbone charge densities and hydrophilicities.
Some of the most widely studied synthetic degradable polyelectrolytes are based on polyphosphazene and poly(β-amino ester) scaffolds. Anionic and cationic derivatives of poly(phosphazene) are promising vaccine adjuvants and nucleic acid delivery agents, respectively; however, complex monomer syntheses and harsh polymerization conditions limit the types of chemical functionality that may be introduced into these materials. Synthesized by the Michael addition polymerization of diamines with diacrylates, poly(beta-amino esters) comprise a modular platform of polycationic materials exhibiting highly variable hydrophilicities and tunable degradabilities depending on the specific monomers used. Various groups have demonstrated the utility of these materials as components in drug delivery vehicles and in erodible polyelectrolyte multilayer films for therapeutic small molecule and nucleic acid delivery. In spite of the demonstrated potential of poly(beta-amino esters), their widespread utility in biomedical applications is curtailed by synthetic difficulties associated with tuning the charge density along the polymer backbone.
What is needed are readily accessible monomer and polymer platforms that provide new materials, particularly for biological applications.