title: Polymer-conjugated inhibitors of tumor necrosis factor-α for local control of inflammation.
abstract: Burns, chronic wounds, osteoarthritis, and uveitis are examples of conditions characterized by local, intense inflammatory responses that can impede healing or even further tissue degradation. The most powerful anti-inflammatory drugs available are often administered systemically, but these carry significant side effects and are not compatible for patients that have underlying complications associated with their condition. Conjugation of monoclonal antibodies that neutralize pro-inflammatory cytokines to high molecular weight hydrophilic polymers has been shown to be an effective strategy for local control of inflammation. Lead formulations are based on antibody inhibitors of tumor necrosis factor-α conjugated to hyaluronic acid having molecular weight greater than 1 MDa. This review will discuss fundamental aspects of medical conditions that could be treated with these conjugates and design principles for preparing these cytokine-neutralizing polymer conjugates. Results demonstrating that infliximab, an approved inhibitor of tumor necrosis factor-α, can be incorporated into the conjugates using a broad range of water-soluble polymers are also presented, along with a prospectus for clinical translation.
authors.affiliation: Department of Biomedical Engineering; Carnegie Mellon University; Pittsburgh, PA USA; Department of Chemistry; Carnegie Mellon University; Pittsburgh, PA USA.
authors.forename: Newell R
authors.initials: NR
authors.lastname: Washburn
authors.affiliation: Department of Chemistry; Carnegie Mellon University; Pittsburgh, PA USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Prata
authors.affiliation: Department of Biomedical Engineering; Carnegie Mellon University; Pittsburgh, PA USA.
authors.forename: Emily E
authors.initials: EE
authors.lastname: Friedrich
authors.affiliation: Department of Chemistry; Carnegie Mellon University; Pittsburgh, PA USA.
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Ramadan
authors.affiliation: Department of Chemistry; Carnegie Mellon University; Pittsburgh, PA USA.
authors.forename: Allison N
authors.initials: AN
authors.lastname: Elder
authors.affiliation: Department of Biomedical Engineering; Carnegie Mellon University; Pittsburgh, PA USA.
authors.forename: Liang Tso
authors.initials: LT
authors.lastname: Sun
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D016503:Drug Delivery Systems; D006801:Humans; D006820:Hyaluronic Acid / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy*; D000069285:Infliximab; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D011108:Polymers; D014409:Tumor Necrosis Factor-alpha; D006820:Hyaluronic Acid; D000069285:Infliximab
keywords: drug delivery; hyaluronic acid; infliximab; polymer; therapeutic antibody; tumor necrosis factor-alpha; wound healing
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