Marcela Díaz, Lucía Vaamonde, Federico Dajas
Quercetin, a representative flavonoid, is a potent antioxidant and anti-inflammatory molecule that modulates cellular signals and promotes the expression of survival proteins. In spite of this pharmacological profile, the administration of quercetin to experimental Parkinson´s Disease (PD) models has shown controversial results. Low plasma and brain bioavailability following acute administration due to high metabolization rates and poor crossing of the blood brain barrier have been proposed as explanations. In an attempt to surpass these difficulties, we developed lecithin/cholesterol/2-hydroxypropyl-β-cyclodextrin nanosomes of quercetin (NSQ), to test whether the use of an appropriate vehicle can provide metabolic protection and ease the delivery to the brain to achieve active brain concentrations that assure the survival of neurons in a model of PD. As an in vivo experimental test of the effectiveness of NSQ, we administered it after the 6-hydroxydopamine (6-OHDA) injection in the Substantia Nigra (SN) in a model of PD in rats. The nanosomes were effective in delivering quercetin to the brain via both intravenous and intraperitoneal routes of administration and prevented the increase in malondialdehyde in the SN provoked by the lesion. The decrease in striatal dopamine levels following 6-OHDA administration in SN was significantly ameliorated following NSQ treatment one hour after the toxin injection. The empty nanosomes prevented corpus striatum (CS) dopamine decrease when given in multiple, repeated doses at 1, 24, 48 and 72 hours after 6 OHDA. In conclusion, nanosomes of quercetin achieve brain concentrations of free quercetin and show protective effects in experimental Parkinson´s Disease at the terminal field (CS) of lesioned Substantia Nigra neurons that did not recover after treatment.
