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

Abstract

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)