title: Hybrid polyglycerols with long blood circulation: synthesis, biocompatibility, and biodistribution.
abstract: Multifunctional polymers with defined structure and biocompatibility are critical to the development of drug delivery systems and bioconjugates. In this article, the synthesis, in vitro blood compatibility, cell viability, in vivo circulation, biodistribution, and clearance of hybrid copolymers based on linear and branched polyglycerol are reported. Hybrid polyglycerols (M(n) ≈ 100 kDa) are synthesized with different compositions (15-80 mol% linear polyglycerol). Relatively small hydrodynamic size and radius of gyration of the hybrid polyglycerols suggest that they are highly compact functional nanostructures. The hybrid polyglycerols show excellent blood compatibility as determined by measuring their effects on blood coagulation, red blood cell aggregation, hemolysis, platelet, and complement activation. The cell viability in presence of hybrid polyglycerols is excellent up to 10 mg mL(-1) concentration and is similar to both dextran and polyvinyl alcohol. Furthermore, tritium labeled hybrid polyglycerol shows long blood circulation (t(1/2β)= 34 h) with minimal organ accumulation in mice. Multifunctionality, compact nature, biocompatibility, and the long blood circulation make these polymers attractive for the development of bioconjugates and drug delivery systems.
authors.affiliation: Centre for Blood Research, Department of Pathology and Laboratory Medicine, 2350 Health Sciences Mall, Vancouver BC, V6T 1Z3, Canada; Department of Chemistry, The University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver BC, V6T 1Z3, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Imran ul-haq
authors.forename: Benjamin F L
authors.initials: BF
authors.lastname: Lai
authors.forename: Jayachandran N
authors.initials: JN
authors.lastname: Kizhakkedathu
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004903:Erythrocyte Aggregation / Q000187:drug effects; D005260:Female; D005990:Glycerol / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D006461:Hemolysis / Q000187:drug effects; D018056:Hemorheology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry; D015539:Platelet Activation / Q000187:drug effects; D011108:Polymers / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution; D014316:Tritium
chemical_list: D001672:Biocompatible Materials; D011108:Polymers; D014316:Tritium; C043941:polyglycerol; D005990:Glycerol
keywords: biodistribution; blood circulation; blood compatibility; cell viability; linear-branched hybrid polyglycerol