1. Preparation and properties of branched oligoglycerol modifiers for stabilization of liposomes.
- Author
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Ishihara A, Yamauchi M, Kusano H, Mimura Y, Nakakura M, Kamiya M, Katagiri A, Kawano M, Nemoto H, Suzawa T, and Yamasaki M
- Subjects
- Adsorption drug effects, Animals, Chemistry, Pharmaceutical methods, Doxorubicin pharmacokinetics, Drug Stability, Glycerol chemistry, Injections, Intravenous, Liposomes blood, Liposomes chemical synthesis, Liposomes chemistry, Male, Phosphatidylethanolamines chemistry, Phospholipids chemical synthesis, Rats, Rats, Inbred Strains, Streptavidin chemistry, Surface Properties, Blood Proteins pharmacokinetics, Drug Compounding methods, Glycerol analogs & derivatives, Liposomes administration & dosage
- Abstract
We examined the effect on drug delivery of liposomes with surfaces that were modified with branched oligoglycerols (BGLs) and explored possible formulation advantages to increase drug exposure. BGL012 is a branched oligoglycerol derivative with a cascade-like structure of 12 glycerol units, characterized as a widely spread structure in aqueous solution. We prepared BGL-phospholipid derivatives (BGL-PEs), including BGL012, by coupling 1,2-distearoylphosphatidylethanolamine to BGLs. BGL012-PE modification of the liposomes (BGL012L) achieved a long circulation time after intravenous injection in rats. The circulation lifetime of BGL012L was almost the same as that of polyethylene glycol (PEG)-modified liposomes. The surface of BGL012L induced the formation of a fixed aqueous layer and reduced protein adsorption on the liposome surface, without strong interference with the binding reaction on the liposome. Thus, the newly synthesized branched oligoglycerol derivatives are considered to have useful hydrophilic and physical properties for modifying the liposome surface to increase drug exposure., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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