Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble formulation

Biofactors. 2003;18(1-4):173-83. doi: 10.1002/biof.5520180220.

Abstract

We have derivatised alpha-tocopherol (vitamin E) to a water-soluble polyoxyethanyl-alpha - tocopheryl sebacate (PTS) and discovered that it formed a non-covalent complex with CoQ10 at a molar ratio of 2:1 (PTS-CoQ10). This complex was water-soluble and remained stable for extended periods of time. After oral delivery of the formulation into rats PTS was hydrolysed to vitamin E and elevated levels of both vitamin E and CoQ10 in blood plasma were detected within 1 h. Thus, this aqueous formulation contains a combination of two potent antioxidants. The formulation's efficacy was tested against ischemic brain damage caused by a transient (8 min) bilateral occlusion of the common carotid arteries in rats. The animals received PTS-CoQ10 by two intraperitoneal injections given immediately after ischemia and 3 h later and the brain damage was assessed up to 12 days post-ischemia. A significant neuroprotection was observed in the CA1 hippocampal region, for example at 12 days approximately 50% of CA1 neurons were still alive in the treated animals versus less than 5% in the non-treated group. Our data is consistent with previously published observations indicating the therapeutic potential of antioxidants for treatments of ischemia/reperfusion injuries and the formulation described here is particularly appropriate for the application in acute conditions, such as stroke or cardiac arrest.

MeSH terms

  • Acetates
  • Alkanes / chemistry
  • Animals
  • Antioxidants / administration & dosage*
  • Biological Availability
  • Brain Ischemia / drug therapy
  • Brain Ischemia / pathology
  • Coenzymes
  • Ethylamines / chemistry
  • Kinetics
  • Male
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage
  • Polyethylene Glycols / chemistry
  • Prosencephalon
  • Rats
  • Rats, Sprague-Dawley
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / chemistry*
  • Ubiquinone / metabolism*
  • alpha-Tocopherol / administration & dosage
  • alpha-Tocopherol / analogs & derivatives
  • alpha-Tocopherol / chemistry*
  • alpha-Tocopherol / metabolism*
  • alpha-Tocopherol / pharmacokinetics

Substances

  • Acetates
  • Alkanes
  • Antioxidants
  • Coenzymes
  • Ethylamines
  • Neuroprotective Agents
  • polyoxyethanyl-alpha-tocopheryl sebacate
  • sebacoyl chloride
  • Ubiquinone
  • Polyethylene Glycols
  • ethyl acetate
  • coenzyme Q10
  • alpha-Tocopherol
  • triethylamine