Multiparticulate drug delivery systems for Parkinson′s disease

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Emilia Barcia

Universidad Complutense, Spain

: J Pharm Drug Deliv Res

Abstract

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Ropinirole (RP) is a specific D2 and D3 dopamine receptor agonist indicated for the treatment of Parkinson’s disease (PD) both as monotherapy and in combination with L-dopa in the advanced stages of the disease. New biodegradable RP multiparticulate systems are developed and characterized both in vitro and in vivo. Microparticles were prepared by the solvent-evaporation technique using PLGA (poly-D,L-lactide-co-glycolide acid) resomers 502 and 502H as polymers. Several formulations were prepared with increasing amounts of RP (40, 80 and 120 mg). Mean encapsulation efficiency of RP was >79% in all cases. In vitro release of RP exhibited zero-order kinetics for 2 and 3 weeks for formulations prepared with PLGA 502H and PLGA 502, respectively. The formulation selected was prepared with 120 mg RP and exhibited constant release of the drug for three weeks (K0= 78.23 µg/ day). Evaluation of the efficacy of the formulation selected was performed in an animal model of PD which was developed with the neurotoxin rotenone (RT). RT was given i.p. at a dose of 2 mg/kg/day for 45 days to male Wistar rats. The multiparticulate formulation was administered at two dose levels (7.5 mg/kg and 15 mg/kg) on days 15th and 30th. Moreover RP in solution was daily administered at 1 mg/kg from day 15th when the first symptoms of PD were observed. All treatments were given i.p. After 45 days all animals were sacrificed and brains removed. Brain immunochemistry (Nissl-staining, GFAP and TH immunohistochemistry) and behavioral testing (catalepsy, akinesia, rotarod and swim test) were performed along the study. The results obtained showed that animals receiving the multiparticulate formulation selected at a dose of 15 mg/kg significantly reverted PD-like symptoms, thereby confirming the potential therapeutic interest of this new biodegradable delivery system developed for ropinirole and destined to treat Parkinson´s disease.

Biography

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Emilia Barcia is PhD in Pharmaceutics from the Universidad Complutense de Madrid (UMC), Spain. Her current position is Chairman of the Department of Pharmaceutics at the School of Pharmacy (UMC) and Full Professor. Her main research interests are focused on the development of new controlled drug delivery systems for neurodegenerative disorders as well as population pharmacokinetics studies. She belongs to SPLC-CRS (Spanish-Portuguese Local Chapter of the Controlled Release Society) and to SEFIG (Spanish Society of Pharmaceutics) and has directed more than 12 doctoral thesis and published more than 50 scientific research articles.