title: Semi-permeable coatings fabricated from comb-polymers efficiently protect proteins in vivo.
abstract: In comparison to neutral linear polymers, functional and architecturally complex (that is, non-linear) polymers offer distinct opportunities for enhancing the properties and performance of therapeutic proteins. However, understanding how to harness these parameters is challenging, and studies that capitalize on them in vivo are scarce. Here we present an in vivo demonstration that modification of a protein with a polymer of appropriate architecture can impart low immunogenicity, with a commensurably low loss of therapeutic activity. These combined properties are inaccessible by conventional strategies using linear polymers. For the model protein L-asparaginase, a comb-polymer bio-conjugate significantly outperformed the linear polymer control in terms of lower immune response and more sustained bioactivity. The semi-permeability characteristics of the coatings are consistent with the phase diagram of the polymer, which will facilitate the application of this strategy to other proteins and with other therapeutic models.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
authors.forename: Mi
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich 8091, Switzerland.
authors.forename: Pål
authors.initials: P
authors.lastname: Johansen
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich 8091, Switzerland.
authors.forename: Franziska
authors.initials: F
authors.lastname: Zabel
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.affiliation: 1] Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich (ETH Zurich), Zurich 8093, Switzerland [2] Institut National de la Recherche Scientifique (INRS), EMT Research Center, Varennes, Quebec J3X 1S2, Canada.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Gauthier
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D001215:Asparaginase / Q000008:administration & dosage* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008689:Methacrylates; C524499:polyethylene glycol methacrylate; D011092:Polyethylene Glycols; D001215:Asparaginase