Micro- and Nano-Systems Developed for Tolcapone in Parkinson's Disease.

To date there is no cure for Parkinson's disease (PD), a devastating neurodegenerative disorder with levodopa being the cornerstone of its treatment. In early PD, levodopa provides a smooth clinical response, but after long-term therapy many patients develop motor complications. Tolcapone (TC) is an effective adjunct in the treatment of PD but has a short elimination half-life. In our work, two new controlled delivery systems of TC consisting of biodegradable PLGA 502 (poly (D,L-lactide-co-glycolide acid) microparticles (MPs) and nanoparticles (NPs) were developed and characterized. Formulations MP-TC4 and NP-TC3 were selected for animal testing. Formulation MP-TC4, prepared with 120 mg TC and 400 mg PLGA 502, exhibited a mean encapsulation efficiency (EE) of 85.13%, and zero-order in vitro release of TC for 30 days, with around 95% of the drug released at this time. Formulation NP-TC3, prepared with 10 mg of TC and 50 mg of PLGA 502, exhibited mean EE of 56.69%, particle size of 182 nm, and controlled the release of TC for 8 days. Daily i.p. (intraperitoneal) doses of rotenone (RT, 2 mg/kg) were given to Wistar rats to induce neurodegeneration. Once established, animals received TC in saline (3 mg/kg/day) or encapsulated within formulations MP-TC4 (amount of MPs equivalent to 3 mg/kg/day TC every 14 days) and NP-TC3 (amount of NPs equivalent to 3 mg/kg/day TC every 3 days). Brain analyses of Nissl-staining, GFAP (glial fibrillary acidic protein), and TH (tyrosine hydroxylase) immunohistochemistry as well as behavioral testing (catalepsy, akinesia, swim test) showed that the best formulation was NP-TC3, which was able to revert PD-like symptoms of neurodegeneration in the animal model assayed.

Application of neurotoxin- and pesticide-induced animal models of Parkinson's disease in the evaluation of new drug delivery systems.

Parkinson's disease (PD) is the second most prevalent neuro-degenerative disease after Alzheimer´s disease. It is characterized by motor symptoms such as akinesia, bradykinesia, tremor, rigidity, and postural abnormalities, due to the loss of nigral dopaminergic neurons and a decrease in the dopa-mine contents of the caudate-putamen structures. To this date, there is no cure for the disease and available treatments are aimed at controlling the symptoms. Therefore, there is an unmet need for new treatments for PD. In the past decades, animal models of PD have been proven to be valuable tools in elucidating the nature of the pathogenic processes involved in the disease, and in designing new pharmacological approaches. Here, we review the use of neurotoxin-induced and pesticide-induced animal models of PD, specifically those induced by rotenone, paraquat, maneb, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and 6-OHDA (6-hydroxydopamine), and their application in the development of new drug delivery systems for PD.

Nanotechnology-based drug delivery of ropinirole for Parkinson's disease.

A new drug delivery system is developed for ropinirole (RP) for the treatment of Parkinson's disease (PD) consisting of biodegradable poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs). The formulation selected was prepared with 8 mg RP and 50 mg PLGA 502. This formulation exhibited mean encapsulation efficiency of 74.8 ± 8.2%, mean particle size lower than 155 nm, the zeta potential of -14.25 ± 0.43 mV and zero-order in vitro release of RP (14.13 ± 0.17 µg/h/10 mg NPs) for 5 d. Daily doses of the neurotoxin rotenone (2 mg/kg) given i.p. to male Wistar rats induced neuronal and behavioral changes similar to those of PD. Once neurodegeneration was established (15 d) animals received RP in saline (1 mg/kg/d for 35 d) or encapsulated within PLGA NPs (amount of NPs equivalent to 1 mg/kg/d RP every 3 d for 35 d). Brain histology and immunochemistry (Nissl-staining, glial fibrillary acidic protein and tyrosine hydroxylase immunohistochemistry) and behavioral testing (catalepsy, akinesia, rotarod and swim test) showed that RP-loaded PLGA NPs were able to revert PD-like symptoms of neurodegeneration in the animal model assayed.