title: Maleimide-Functionalized Poly(2-Oxazoline)s and Their Conjugation to Elastin-Like Polypeptides.
abstract: The design of drug delivery systems capable of efficiently delivering poorly soluble drugs to target sites still remains a major challenge. Such materials require several different functionalities; typically, these materials should be biodegradable and nontoxic, nonimmunogenic, responsive to their environment, and soluble in aqueous solution while retaining the ability to solubilize hydrophobic drugs. Here, a polypeptide-polymer hybrid of elastin-like polypeptides (ELPs) and poly(2-oxazoline)s (POx) is reported. This paper describes the chemical synthesis, physical characteristics, and drug loading potential of these novel hybrid macromolecules. A novel method is introduced for terminal functionalization of POx with protected maleimide moieties. Following recovery of the maleimide group via a retro Diels-Alder reaction, the consecutive Michael addition of thiol-functionalized ELPs yields the desired protein-polymer conjugate. These conjugates form nanoparticles in aqueous solution capable of solubilizing the anti-cancer drug paclitaxel with up to 8 wt% loading.
authors.affiliation: Department Chemie, Technische Universität Dresden, Mommsenstr. 4, 01069, Dresden, Germany.
authors.forename: Jonas F
authors.initials: JF
authors.lastname: Nawroth
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, 27708-0281, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McDaniel
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, NC, 27708-0281, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
authors.affiliation: Department Chemie, Technische Universität Dresden, Mommsenstr. 4, 01069, Dresden, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Jordan
authors.affiliation: Department Chemie, Technische Universität Dresden, Mommsenstr. 4, 01069, Dresden, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Luxenhofer
mesh_terms: D004549:Elastin / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D008301:Maleimides; D010080:Oxazoles; D011994:Recombinant Proteins; C577913:poly(2-oxazoline); C043592:maleimide; D004549:Elastin
keywords: bioconjugation; drug delivery systems; elastin-like polypeptides; paclitaxel; ring-opening polymerization