title: Hemospan: design principles for a new class of oxygen therapeutic.
abstract: Hemoglobin-based oxygen carriers have been under development for decades, but safety concerns have prevented commercial approval. Early designs for modified hemoglobins by polymerization or intramolecular cross-linking reactions increased molecular size and decreased oxygen affinity, but all exhibited side effects of vasoconstriction and reduced blood flow. A new strategy has been established by applying principles of oxygen transport to cell-free hemoglobin. Sangart has developed a new oxygen therapeutic, Hemospan, using site-specific, poly(ethylene) glycol conjugation chemistry designed on two principles: (i) increased macromolecular size to prolong intravascular retention time, and (ii) increased oxygen affinity to prevent premature oxygen offloading in arterioles. In contrast to early-generation products, Hemospan infusion maintains normal arteriolar vascular tone and capillary flow. Phase I and Phase II clinical trials have been completed, showing that Hemospan is well-tolerated in humans, with evidence of efficacy to impart hemodynamic stability in surgical patients under anesthesia. Phase III trials in orthopedic surgery have recently completed enrollment in Europe.
authors.affiliation: Sangart, Inc., San Diego, CA, USA. kvandegriff@sangart.com
authors.forename: Kim D
authors.initials: KD
authors.lastname: Vandegriff
authors.forename: Robert M
authors.initials: RM
authors.lastname: Winslow
mesh_terms: D000818:Animals; D001802:Blood Substitutes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015195:Drug Design; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008301:Maleimides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D010100:Oxygen / Q000378:metabolism / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001802:Blood Substitutes; D006454:Hemoglobins; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols; D010100:Oxygen