A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.
The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg/kg), a saline solution of tacrine (5mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.
Iannone
Michelangelo
M
ARPA Calabria, Environmental Epidemiology Centre, CNR-ISN Section of Pharmacology, Complesso Ninì Barbieri, I-88021 Roccelletta di Borgia (CZ), Italy. m.iannone@arpacal.it
Cosco
Donato
D
Cilurzo
Felisa
F
Celia
Christian
C
Paolino
Donatella
D
Mollace
Vincenzo
V
Rotiroti
Domenicantonio
D
Fresta
Massimo
M
D000818:Animals; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000473:pathology; D002199:Capillary Permeability; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology; D018021:Lithium Chloride; D053758:Nanoparticles; D011091:Polyesters; D051381:Rats; D013619:Tacrine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity
D002491:Central Nervous System Agents; D002800:Cholinesterase Inhibitors; D011091:Polyesters; C033616:poly(lactide); D013619:Tacrine; D018021:Lithium Chloride