title: Developing an in situ forming polyphosphate coacervate as a new liquid embolic agent: From experimental design to pilot animal study.
abstract: A radiopaque temporary liquid embolic agent was synthesized from polyphosphate (PP) coacervates and optimized using a design of experiments approach. Variables studied were: strontium substitution (0-15 mol%), barium substitution (0-15 mol%), PP concentration and degree of polymerization of the polyphosphate (Dp). The viscosity, radiopacity and cell viability of the resulting coacervates were measured for 60 formulations and response surface modeling was used to determine the optimum coacervate that maximized radiopacity and cell viability. The optimum coacervate made from PP with a large Dp (9.5 g NaPP/100mL, 2.2 mol% Sr, 9 mol% Ba and 3.8 mol% Ca) was taken forward to a pilot animal trial. In this rabbit model, PP embolic agent successfully occluded the central auricular artery with promising biocompatibility. Further study is required to optimize the cohesiveness and clinical effectiveness of PP as an in situ setting temporary embolic agent.
  
  
  CONCLUSIONS
  This article describes the development of a new radiopaque temporary liquid embolic agent from the optimization using design of experiments to a pilot animal study. Embolization is a minimally invasive interventional radiology procedure used to block blood flow in a targeted blood vessel. This procedure is used to treat many conditions including: tumors, aneurysms and arteriovenous malformations. Currently, no inherent radiopaque embolic agents are available in the clinic, which would allow for direct imaging of the material during the procedure and follow up treatment.
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada; Faculty of Dentistry, Department of Applied Oral Sciences, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada.
authors.forename: Arash
authors.initials: A
authors.lastname: Momeni
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada.
authors.forename: Esther Mae
authors.initials: EM
authors.lastname: Valliant
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada.
authors.forename: Ellen Patricia
authors.initials: EP
authors.lastname: Brennan-Pierce
authors.affiliation: Faculty of Medicine, Department of Diagnostic Radiology, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada.
authors.forename: Jai Jai Shiva
authors.initials: JJS
authors.lastname: Shankar
authors.affiliation: Faculty of Medicine, Department of Diagnostic Radiology, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Abraham
authors.affiliation: Faculty of Medicine, Department of Pathology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada.
authors.forename: Patricia
authors.initials: P
authors.lastname: Colp
authors.affiliation: School of Biomedical Engineering, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada; Faculty of Dentistry, Department of Applied Oral Sciences, Dalhousie University, Halifax, Nova Scotia B3H 3J5, Canada; Faculty of Medicine, Department of Diagnostic Radiology, QEII Health Sciences Centre, Halifax, Nova Scotia B3H 3A7, Canada. Electronic address: Mark.Filiaggi@dal.ca.
authors.forename: Mark Joseph
authors.initials: MJ
authors.lastname: Filiaggi
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004423:Ear / Q000098:blood supply; D004621:Embolization, Therapeutic; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D008962:Models, Theoretical; D041681:NIH 3T3 Cells; D010865:Pilot Projects; D011122:Polyphosphates / Q000494:pharmacology*; D011817:Rabbits; D012107:Research Design; D012996:Solutions; D040521:Subcutaneous Tissue / Q000187:drug effects; D014783:Viscosity
chemical_list: D011122:Polyphosphates; D012996:Solutions
keywords: Design of experiments (DOE); Liquid embolic agent; Pilot animal study; Polyphosphate; Radiopaque; Temporary