Liposomes as in-vivo carriers for citicoline: effects on rat cerebral post-ischaemic reperfusion

J Pharm Pharmacol. 1994 Dec;46(12):974-81. doi: 10.1111/j.2042-7158.1994.tb03252.x.

Abstract

Citicoline is a therapeutic agent widely used in the treatment of brain injury, for example in cerebrovascular disease or traumatic accidents. Unfortunately, the strong polar nature of this drug prevents it crossing the blood-brain barrier. In this paper, the possibility of efficiently trapping citicoline in liposomes to improve its therapeutic effects is reported. The citicoline-encapsulation efficiency, drug leakage and size analysis of various liposome systems were studied. The real therapeutic effectiveness of these citicoline liposome formulations was evaluated by biological assay. The effects of free and liposome encapsulated citicoline on survival rate of ischaemic reperfused male Wistar rats (80-100 g) were investigated. Of the phospholipid mixtures used in citicoline liposome formulation the best in terms of delivery and therapeutic effects was 1,2-dipalmitoyl-sn-glycero-phosphocholine: dipalmitoyl-DL-alpha-phosphatidyl-L-serine:cholesterol (7:4:7 molar ratio). This phospholipid mixture was also assayed for brain conjugated diene levels in rats, since this parameter is an index of lipid peroxidation in rat cerebral cortex during post-ischaemic reperfusion. A citicoline-loaded phospholipid mixture has produced an increase in rat survival rate of about 24% and a reduction in diene levels of 60%, compared to the free drug.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1,2-Dipalmitoylphosphatidylcholine / chemistry
  • 1,2-Dipalmitoylphosphatidylcholine / metabolism
  • Animals
  • Blood-Brain Barrier
  • Brain Ischemia / drug therapy*
  • Cerebral Cortex / drug effects
  • Cholesterol / chemistry
  • Cholesterol / metabolism
  • Chromatography, High Pressure Liquid
  • Cytidine Diphosphate Choline / administration & dosage*
  • Cytidine Diphosphate Choline / pharmacokinetics
  • Cytidine Diphosphate Choline / pharmacology
  • Cytidine Diphosphate Choline / therapeutic use
  • Disease Models, Animal
  • Drug Carriers
  • Drug Compounding
  • Drug Delivery Systems*
  • Drug Evaluation
  • Lactates / metabolism
  • Lactic Acid
  • Lipid Peroxidation / drug effects
  • Liposomes
  • Male
  • Phosphatidylserines / chemistry
  • Phosphatidylserines / metabolism
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / mortality
  • Survival Rate

Substances

  • Drug Carriers
  • Lactates
  • Liposomes
  • Phosphatidylserines
  • 1,2-Dipalmitoylphosphatidylcholine
  • dipalmitoylphosphatidylserine
  • Lactic Acid
  • Cytidine Diphosphate Choline
  • Cholesterol