title: An effective novel delivery strategy of rasagiline for Parkinson's disease.
abstract: This is the first report on the efficacy of a new controlled release system developed for rasagiline mesylate (RM) in a rotenone-induced rat model of Parkinson's disease (PD). PLGA microspheres in vitro released RM at a constant rate of 62.3 μg/day for two weeks. Intraperitoneal injection of rotenone (2 mg/kg/day) to Wistar rats produced typical PD symptoms. Catalepsy, akinesia and swim tests outcomes in animals receiving RM either in solution or within microspheres showed a reversal in descent latency when compared to rotenone-treated animals, being this reversal specially pronounced in animals receiving RM microspheres (dose equivalent to 1 mg/kg/day RM injected i.p. every 15 days). Nissl-staining of brain sections showed selective degeneration of the substantia nigra (SNc) dopaminergic neurons in rotenone-treated animals which was markedly reverted by RM microspheres. PET/CT with (18)F-DG resulted in mean increases of accumulation of radiotracer in striatum and SNc of around 40% in animals treated with RM microspheres which also had significant beneficial effects on Bcl-2, Bax, TNF-α mRNA and SOD2 levels as detected by real-time RT-PCR. Our results confirm the robust effect achieved by the new controlled release system developed for RM which exhibited better in vivo efficacy than RM given in solution.
authors.affiliation: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Fernández
authors.forename: Sofía
authors.initials: S
authors.lastname: Negro
authors.forename: Karla
authors.initials: K
authors.lastname: Slowing
authors.forename: Ana
authors.initials: A
authors.lastname: Fernández-Carballido
authors.forename: Emilia
authors.initials: E
authors.lastname: Barcia
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18; D007189:Indans / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D064847:Multimodal Imaging / Q000379:methods; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone; D014057:Tomography, X-Ray Computed
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D007189:Indans; C031967:rasagiline; D012402:Rotenone; D019788:Fluorodeoxyglucose F18; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid