title: Efficacy of Ropinirole-Loaded PLGA Microspheres for the Reversion of Rotenone- Induced Parkinsonism.
abstract: A new controlled delivery system has been developed for ropinirole (RP) for the treatment of Parkinson´s Disease (PD) consisting in PLGA microparticles (MPs) which exhibited in vitro constant release of RP (78.23 µg/day/10 mg MPs) for 19 days. The neuroprotective effects of RP released from MPs were evaluated in SKN-AS cells after exposure to rotenone (20 µM). Cell apoptosis was significantly reduced by RP (100-120 µM). Daily doses of rotenone (2 mg/kg) given i.p. to rats induced neuronal and behavioral changes similar to those of PD. After 15 days, animals received RP in saline (1 mg/kg/day for 45 days) or as MPs at two dose levels (amount of MPs equivalent to 7.5 mg/kg or 15 mg/kg RP given on days 15 and 30). Brain immunochemistry (Nisslstaining, GFAP and TH immunohistochemistry) and behavioral testing (catalepsy, akinesia, rotarod and swim test) showed that animals receiving RP either in solution or encapsulated within the MPs reverted the PD symptoms with the best results obtained in animals receiving RP microspheres at the highest dose assayed, thereby confirming the potential therapeutic interest of the new RP delivery system.
authors: Departamento de Farmacia y Tecnología Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid. Spain.
authors: Sofia
authors: S
authors: Negro
authors: Departamento de Farmacia y Tecnología Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid. Spain.
authors: Liudmilla
authors: L
authors: Boeva
authors: Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid. Spain.
authors: Karla
authors: K
authors: Slowing
authors: Departamento de Farmacia y Tecnología Farmaceutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid. Spain.
authors: Ana
authors: A
authors: Fernandez-Carballido
authors: Departamento de Farmacologia, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid. Spain.
authors: Luis
authors: L
authors: Garcia-García
authors: Dpto. Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Plaza Ramon y Cajal s/n, 28040 Madrid. Spain.
authors: Emilia
authors: E
authors: Barcia
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007306:Insecticides / Q000633:toxicity; D019344:Lactic Acid / Q000008:administration & dosage*; D008297:Male; D008863:Microspheres; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000633:toxicity*; D016896:Treatment Outcome
chemical_list: D000978:Antiparkinson Agents; D007211:Indoles; D007306:Insecticides; C046649:ropinirole; D012402:Rotenone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA; Parkinson´s disease; Ropinirole; brain immunochemistry; microspheres; rotenone