PEGylated dextran as long-circulating pharmaceutical carrier.
Dextran-polyethylene glycol (PEG) conjugates were synthesized by activating dextran hydroxy groups with carbonyldiimidazole, introducing amino groups by attaching ethylenediamine, and reacting amino groups with a succinimidyl-activated derivative of PEG. Conjugates with an average of 12 and 21 PEG (5 kDa) residues per single dextran (73 kDa) molecule were prepared. These conjugates have circulation half-lives of 5.3 h and 7.0 h, respectively, compared to 4.0 h for non-PEGylated dextran. The modification of dextran with PEG inhibits the uptake of polymer by the major organ of the reticuloendothelial system, the liver. Dextran-PEG conjugates may represent a convenient platform for long-circulating pharmaceutical preparations.
Lukyanov
Anatoly N
AN
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, 312 Mugar Building, Northeastern University, Boston, MA 02115, USA.
Sawant
Rishikesh M
RM
Hartner
William C
WC
Torchilin
Vladimir P
VP
D000818:Animals; D003911:Dextrans / Q000097:blood / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D005260:Female; D006207:Half-Life; D051379:Mice; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D003911:Dextrans; D004337:Drug Carriers; D011108:Polymers; D011092:Polyethylene Glycols