Hydrophobically derivatized hyperbranched polyglycerol as a human serum albumin substitute.
There is a huge clinical demand for Human Serum Albumin (HSA), with a world market of approximately $1.5B/year. Concern over prion and viral transmission in the blood supply has led to a need for safer substitutes and offers the opportunity for development of materials with enhanced properties over the presently available plasma expanders. We report here the synthesis and testing of a new synthetic plasma expander that can replace not only the osmotic and volume expansion properties of HSA but, uniquely, its binding and transport properties. We have synthesized several hyperbranched polyglycerols derivatized with hydrophobic groups and short poly(ethylene glycol) (PEG) chains. The hydrophobic groups provide regions for binding fatty acids and other hydrophobic materials while PEG imparts the necessary protection from host defense systems and enhances circulation longevity. These polymers, being hyperbranched, have only a small effect on plasma viscosity. We have shown in vitro that our materials bind 2-3 moles palmitic acid per mole, do not activate the platelet, coagulation or complement systems and do not cause red cell aggregation. In mice these materials are non-toxic with circulation half-lives as high as 34h, controllable by manipulating the molecular weight and the degree of PEG derivatization.
Kainthan
Rajesh K
RK
Centre for Blood Research, Life Sciences Centre, 2350 Health Sciences Mall, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Janzen
Johan
J
Kizhakkedathu
Jayachandran N
JN
Devine
Dana V
DV
Brooks
Donald E
DE
D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism; D001798:Blood Proteins / Q000737:chemistry; D005260:Female; D005990:Glycerol / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D015539:Platelet Activation / Q000187:drug effects; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D012709:Serum Albumin; D018675:Toxicity Tests; D014783:Viscosity
D001672:Biocompatible Materials; D001798:Blood Proteins; D011108:Polymers; D012709:Serum Albumin; C043941:polyglycerol; D005990:Glycerol