Evaluation of rat striatal L-Dopa and DA concentration after intraperitoneal administration of L- Dopa prodrugs in liposomal formulations

Parkinson’s disease is a neurodegenerative disease and its symptoms are relieved by administration of l-dopa (LD), which is
converted by neuronal aromatic l-aminoacid decarboxylase (AADC), restoring dopamine (DA) levels in surviving neurons. In
order to minimize unfavourable side effects, we studied new dimeric LD derivatives, as potential prodrugs for Parkinson’s
therapeutic treatment. To improve the bioavailability of the synthesized prodrugs, they were encapsulated in unilamellar
liposomes of dimiristoylphosphatidylcholine (DMPC) and cholesterol (CHOL). In vivo microdialysis was used to monitor the
striatal LD and DA concentrations after i.p. administration of new delivery systems. Bioavailability evaluation was performed
by means of the HPLC-EC method. The striatal levels of LD and DA were remarkably elevated after i.p. administration of
liposomal formulation of prodrug (+)-1b ([(O,O-diacetyl)-l-dopa-methylester]-succinyldiamide). This formulation showed
about 2.5-fold increase in the basal levels of DA in dialysate rat striatum, suggesting that liposomal formulation of (+)-1b
significantly increases LD and DA concentrations with respect to equimolar administration of LD itself or free prodrug (+)-1b.