Graft copolymer polyelectrolyte complexes for drug delivery

摘要

Graft copolymer polyelectrolyte complexes are disclosed for the efficient delivery of anionic, cationic or polyelectrolyte therapeutic agents into biological cells, and for maintaining the biological activity of these molecules while in serum and other aqueous environments are provided. Such complexes comprise (1) an anionic graft copolymer containing an anionic polymer backbone, with pendent carboxylic acid groups and pendant chains containing amphipathic or hydrophilic polymers covalently bonded to a portion of the pendant carboxylic acid groups, (2) one or more anionic, cationic or polyelectrolyte therapeutic agents, and (3) optionally a liposome optionally containing an additional therapeutic agent. Also disclosed are functional nanoparticles containing the complexes.

主权项

1. A graft copolymer polyelectrolyte complex comprising:
(1) an anionic graft copolymer comprising:
(i) a backbone comprising a poly(alkylacrylic acid); and(ii) one or more polyetheramine pendent chains covalently attached to said copolymer backbone as amides of acrylic acid groups, wherein said pendent chains predominantly comprise ethylene oxide repeating units; wherein said copolymer has a graft density between about 0.1 and about 25 mole percent; (2) one or more anionic, cationic or polyelectrolyte therapeutic agents; and (3) optionally, a liposome which optionally comprises a further therapeutic agent;wherein when said anionic, cationic or polyelectrolyte therapeutic agent is a polynucleotide molecule, said liposome, optionally comprising said further therapeutic agent, is also present; and wherein said pendent chains further comprise one or more ligands that target a microbial biofilm or a planktonic microbe; or said pendent chains further comprise one or more ligands which comprise a phosphonate molecule that targets bone tissue.