Lipid nanocarriers containing a levodopa prodrug with potential antiparkinsonian activity

This paper describes the production, characterization and in vivo activity of lipid nanocarriers (LN) containing alevodopa prodrug (LD-PD) with therapeutic potential in Parkinson's disease. LD is the mainstay of the pharma-cotherapy of Parkinson's disease. However, after a good initial response, motorfluctuations, dyskinesia andloss ofefficacy,develop over time, partlydueto oscillationsinplasmaand brain levelsofthedrug. LD-PD was pro-duced with the aim of prolonging the pharmacological activity of LD. To improve solubility, and simultaneouslyprovide a long lasting release and therapeutic efficacy, the prodrug was formulated in tristearin/lecithin LN.The obtained formulation was homogeneous in particle size and remained stable for up to 2 months from prep-aration. For the threedifferent tested LD concentrations, namely 1.25, 2.5 and 5.0 mg/ml, the morphological char-acterization revealed no substantial differences between unloaded and LD-PD loaded LN. The calorimetric testshowed an interaction between the lipid phase and the loaded prodrug. In vitro studies using the dialysis methodand enzymatic degradation procedure showed that the LD-PD loaded LN provided a controlled prodrug release.Finally, two behavioural tests specific to akinesia (bar test) or akinesia/bradykinesia (drag test) performed in 6-hydroxydopamine hemilesioned mice (a model of Parkinson's disease) demonstrated that the LD-PD loaded LNattenuated parkinsonian disabilities, showing a slightly reduced maximal efficacy but a longer lasting action (upto 24 h) than an equal dose of LD. We conclude that LD-PD loaded LN may represent a future LD formulation use-ful in Parkinson's disease therapy.