title: Unique technology for solubilization and delivery of highly lipophilic bioactive molecules.
abstract: We have produced a family of novel carriers enabling water solubilization of highly lipophilic molecules. The compound carriers were synthesized by conjugating polyethylene glycol to alpha-tocopherol, tocotrienols, beta-sitosterol or cholesterol via an alkanedioyl linker. These PEG- conjugates were amphiphilic and formed stable non-covalent complexes (nanomicelles) with a wide range of molecules including vitamins, carotenoids, ubiquinones, poly-unsaturated fatty acids and polyene macrolide antibiotics. The resulting formulations were water-soluble, non-toxic and had excellent stability. This solubilization method represents a major advance in the delivery of lipophilic molecules and could be used to reformulate drugs with near term patent expiry or those that have failed clinical trials due to low solubility. Furthermore, the technology could also be applied for delivery of active ingredients for dietary supplement, functional food, cosmetic and animal health industries.
authors.affiliation: Neurogenesis and Brain Repair Group, Institute for Biological Sciences, National Research Council of Canada, Ottawa Ont., Canada K1A 0R6.
authors.forename: Henryk
authors.initials: H
authors.lastname: Borowy-Borowski
authors.forename: Caroline
authors.initials: C
authors.lastname: Sodja
authors.forename: John
authors.initials: J
authors.lastname: Docherty
authors.forename: P Roy
authors.initials: PR
authors.lastname: Walker
authors.forename: Marianna
authors.initials: M
authors.lastname: Sikorska
mesh_terms: D000818:Animals; D001682:Biological Availability; D002318:Cardiovascular Diseases / Q000139:chemically induced; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D019169:Jurkat Cells; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D011090:Polyenes / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013261:Sterols / Q000737:chemistry; D014810:Vitamin E / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008055:Lipids; D004364:Pharmaceutical Preparations; D011090:Polyenes; D013261:Sterols; D014810:Vitamin E; D011092:Polyethylene Glycols