title: Disulfide-crosslinked polyion micelles for delivery of protein therapeutics.
abstract: New protein delivery systems are needed that efficiently encapsulate proteins and avoid formulation processes that affect protein structure and function. We have developed a protein delivery system termed disulfide-crosslinked polyion micelles (DCPMs), which consist of nanocomplexes formed by electrostatic self-assembly of a protein with a poly(ethylene glycol)-poly(L-lysine) block copolymer (PEG-PLL). The PEG-PLL amines are modified with crosslinkable dithiopyridine groups, using a Michael addition reaction that preserves the positive charges on the PLL chain to optimize polyionic complexation and disulfide crosslinking. DCPMs for vaccine delivery were prepared with ovalbumin and immunostimulatory CpG-DNA and are designed to release the vaccine intracellularly through reduction of disulfide crosslinks. DCPMs were also developed as a long-circulating enzyme carrier that maintains the enzymatic activity of the anti-oxidant enzyme catalase within the micelle core. Ovalbumin and catalase were each modified with SPDP to tether the protein in the micelle core, resulting in a high degree of protein retention under SDS-PAGE. DCPMs efficiently encapsulate and retain functional proteins in a stable polyionic complex and are a versatile delivery system for enzymes, vaccine antigens, and other protein therapeutics.
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Heffernan
authors.forename: Niren
authors.initials: N
authors.lastname: Murthy
mesh_terms: D003432:Cross-Linking Reagents / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis*; D004339:Drug Compounding / Q000379:methods; D007477:Ions; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D011506:Proteins / Q000737:chemistry* / Q000627:therapeutic use*
chemical_list: D003432:Cross-Linking Reagents; D004220:Disulfides; D004337:Drug Carriers; D007477:Ions; D008823:Micelles; D011506:Proteins