Graft copolymer polyelectrolyte complexes for delivery of cationic antimicrobial peptides.
Peptides have enormous potential as therapeutic agents for the treatment of infection, in immunomodulation and for other medical applications, but their hydrolytic degradation in biological fluids is a serious limitation to their in vivo performance. Here we demonstrate the potential utility of polyelectrolyte nanoparticle complexes of novel self-assembling anionic graft copolymers for protecting peptides from degradation in human plasma. The anionic graft copolymers are synthesized by covalently attaching pendent polyetheramine chains to poly(alkylacrylic acid) backbones by carbodiimide coupling. The peptide:copolymer nanocomplexes' particle size, zeta-potential, peptide binding, and controlled release of the peptide are shown to be dependent upon the pendent chain graft density, polymer backbone alkyl groups (propyl vs. methyl), and the nanocomplexes' electrostatic charge ratio. The nanocomplexes can provide substantial protection to the bound peptides from degradation in human plasma for at least 24 h and, in standard microbiological assays are shown to retain some or all of the peptide's antimicrobial activity against a clinically relevant strain of Staphylococcus aureus.
U.S. Army Institute of Surgical Research, 3698 Chambers Pass, Fort Sam Houston, Texas 78234, USA.
Krista L
KL
Niece
Asa D
AD
Vaughan
David I
DI
Devore
D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage* / Q000097:blood; D001672:Biocompatible Materials / Q000737:chemistry*; D016503:Drug Delivery Systems; D004573:Electrolytes / Q000737:chemistry; D006801:Humans; D008422:Materials Testing; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects
D023181:Antimicrobial Cationic Peptides; D001672:Biocompatible Materials; D004573:Electrolytes; D011108:Polymers
cationic antimicrobial peptides; graft copolymers; human plasma degradation; poly(alkylacrylic acid); polyelectrolyte complexes