Delivery of protein therapeutics and vaccines using their multivalent complexes with synthetic polyelectrolytes

Clinical applications of protein and peptide-based therapeutics and vaccines are rapidly expanding. However, the development of promising new product candidates is often hindered by unfavorable pharmacokinetic profiles, which necessitate the implementation of drug delivery systems to improve protein stability and bioavailability. Non-covalent modification of proteins with synthetic polyelectrolytes, which relies on the strength of cooperative multivalent interactions, may offer potential advantages. In contrast to commonly employed covalent conjugation or microencapsulation methodologies, this technology offers dynamic protection of the protein thereby minimizing the loss of its biological activity, enabling "mix-and-match" formulation approaches, reducing manufacturing costs and simplifying regulatory processes. The range of potential life sciences applications ranges from immunopotentiation and vaccine delivery systems to long-circulating stealth biotherapeutics. This review analyses current technology in the context of intended clinical indications and discusses various synthetic and formulation approaches leading to supramolecular complexation. It evaluates dynamic interactions of complexes with constituents of physiological compartments and attempts to identify critical factors that can affect future advancement of this paradigm-shifting protein delivery technology.