Transdermal iontophoresis of dopaminergic (pro) drugs : from formulation to in vivo application

Abstract

Parkinson__s disease (PD) is an age-related neurodegenerative disorder. Pharmacotherapy is the first line symptomatic treatment of this neurological disease. Currently Levodopa (L-DOPA) is still considered the drug of first choice, but its possible neurotoxicity and the induction of movement disability after chronic use demand for alternative therapies. An attractive alternative is the use of (semi-)synthetic dopamine agonists. It has been suggested that continuous dopamine receptor stimulation is the best symptomatic treatment of Parkinson__s disease. Therefore the administration of dopamine agonists in a continuous, well-controlled manner by transdermal iontophoresis is an attractive therapeutic strategy in the symptomatic treatment of PD. This dissertation describes the administration of a series of dopamine agonists across the skin using iontophoresis. With iontophoresis a small current is applied across the skin to enhance the transdermal transport of charged molecules. With transdermal iontophoresis a continuous drug administration is achieved. And by adjusting the applied current density it is possible to titrate the dose to the requirements of the patient. In addition, continuous administration results in a continuous stimulation of the dopamine receptors in the striatum. These results demonstrate that transdermal iontophoresis of dopamine agonist is a promising method for the symptomatic treatment of PD.