RESUMO
The aim of this study is to prepare and characterize intranasal delivery of morin hydrate loaded microemulsion for the management of Alzheimer's diseases. After intranasal delivery, brain and blood drug concentrations were found to be higher for optimized morin hydrate loaded microemulsion as compared to plain morin hydrate. Significant (P < 0.05) reduction in assessed pharmacodynamic parameters was observed after intranasal administration of morin hydrate loaded microemulsion as compared to sham control group. Daily chronic treatment with morin loaded microemulsion till the 21st day significantly increased the memory in wistar rats with STZ-induced dementia.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Portadores de Fármacos/química , Flavonoides/administração & dosagem , Flavonoides/química , Administração Intranasal , Liberação Controlada de Fármacos , Emulsões , Flavonoides/uso terapêutico , Concentração de Íons de Hidrogênio , Óleos/química , Tensoativos/químicaRESUMO
Tardive dyskinesia is a type of hyperkinetic movement disorder which consists of abnormal involuntary movements, characterized by orofacial movements. Previous studies suggest that oxidative stress and neuro-inflammation play important role in the pathogenesis of TD. Recently, PPAR-α and PPAR-Ï have been reported as neuroprotective agent in various animal models. The present study investigated the neuroprotective effect of PPAR-Ï agonist, pioglitazone (20 and 40 mg/kg, p.o.) and PPAR-α agonist, fenofibrate (100 and 200mg/kg, p.o.) in an animal model of oral dyskinesia. Oral dyskinesia was induced by chronic administration of haloperidol (1 mg/kg i.p.) for 21 days. Chronic administration of haloperidol significantly increased vacuous chewing movements, tongue protrusions, facial jerking, sniffing and grooming in rats which was dose-dependently inhibited by pioglitazone and fenofibrate. Further, it also decreased % retention of memory in an elevated plus maze test on day 22. Chronic administration of haloperidol also induced oxidative damage and neuroinflammation (TNF-α and IL-1ß) in brain regions. The fenofibrate and pioglitazone were able to reverse the behavioral and biochemical changes induced by haloperidol. Further the study proposed the antioxidant and antiinflammatory effects of both PPAR agonists in this model. We concluded that administration of pioglitazone and fenofibrate individually or in combination along with antipsychotic in the treatment of schizophrenia, prevent or delay the symptoms of oral dyskinesia.