Intranasal mucoadhesive microemulsion of tacrine to improve brain targeting

Alzheimer Dis Assoc Disord. Apr-Jun 2008;22(2):116-24. doi: 10.1097/WAD.0b013e318157205b.

Abstract

The aim of the investigation was to prepare and characterize microemulsion/mucoadhesive microemulsion of tacrine (TME/TMME), assess its pharmacokinetic and pharmacodynamic performances for brain targeting and for improvement in memory in scopolamine-induced amnesic mice. The TME was prepared by the titration method and characterized. Biodistribution of tacrine solution and formulations after intravenous and intranasal administrations were evaluated using 99m Tc as marker. From the data, the pharmacokinetic parameters, drug targeting efficiency, and direct nose-to-brain drug transport were calculated. To confirm drug localization in brain gamma scintigraphy in rabbits was performed. Lower Tmax values (60 min) after intranasal compared with intravenous administration (120 min) suggested selective nose-to-brain transport. The brain bioavailability of tacrine after intranasal TMME compared with intranasal tacrine solution was found to be 2-fold higher indicating larger extent of distribution of the drug to brain with intranasal TMME. Rabbit brain scintigraphy also showed higher uptake of drug into the brain after intranasal administration. The results demonstrated rapid and larger extent of transport of tacrine into the mice brain and fastest regain of memory loss in scopolamine-induced amnesic mice after intranasal TMME. Hence, results are suggestive of possible role of intranasal tacrine delivery in treating Alzheimer's patients.

Publication types

  • Review

MeSH terms

  • Administration, Intranasal
  • Alzheimer Disease / drug therapy*
  • Animals
  • Brain / metabolism*
  • Cholinesterase Inhibitors / administration & dosage
  • Cholinesterase Inhibitors / pharmacokinetics*
  • Emulsions
  • Humans
  • Injections, Intravenous
  • Mice
  • Mucous Membrane / drug effects
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / ultrastructure
  • Rabbits
  • Tacrine / administration & dosage
  • Tacrine / pharmacokinetics*
  • Tissue Adhesives
  • Tomography, Emission-Computed

Substances

  • Cholinesterase Inhibitors
  • Emulsions
  • Tissue Adhesives
  • Tacrine