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Layered double hydroxide-immobilized L-DOPA and benserazide / carbidopa to treat patients with Parkinson's Disease

Grant number: 12/25210-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): April 01, 2013
Effective date (End): March 31, 2014
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
Principal Investigator:Joao Barros Valim
Grantee:Luis Fernando Stucchi da Silva
Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Parkinson's disease is a neurodegenerative disorder characterized by dysfunction or death of dopamine-producing neurons. The most effective treatment for this disease is oral administration of L-dopa, a precursor of dopamine. When ingested, L-dopa is quickly transformed into dopamine by action of dopa decarboxylase. Benserazide and carbidopa inhibit dopa decarboxylase, hindering the peripheral decarboxylation of L-dopa and allowing a larger amount of the drug into the brain. The inclusion of L-dopa in layered double hydroxides (LDH) avoids its decarboxylation and prevents its racemization, which is relevant because the enantiomorph of L-dopa, D-dopa, is toxic. In this project we expect to develop a synthetic route to prepare magnesium-aluminum LDH intercalated with L-dopa and containing benserazida or carbidopa. To make this synthesis feasible, we will use LDH "pillared" with cucurbiturils, CB[n] (neutral macrocyclic), which will allow us to cointercalate anions into the LDH interlayer galleries, spaced by the macrocyclic. We will use thefollowing methods: coprecipitation at constant alkaline pH (to intercalate L-dopa and the CB[n] concomitantly); anion exchange by replacing in dual phase, with the precursor LDH already containing macrocyclic; and indirect contact of LDH pillared with CB[n] with a solution containing L-dopa. The resulting material might be a very effective medicament against Parkinson's disease, since it may increase the half-life of L-dopa in the organism and reduce the unpleasant side effects that persist with the medication used currently. (AU)

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