One-step fabrication of bicompartmental microparticles as a dual drug delivery system for Parkinson’s disease management

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily affecting elderly patients. In order to efficiently manage the symptoms of the disease, controlled and continuous supply of PD drugs [levodopa (LD) and carbidopa (CD)] would be highly beneficial. Currently available commercial tablets are not sufficiently capable of releasing PD drugs in a sustainable fashion. Hence, the purpose of this study was to engineer a carrier system to deliver more than one therapeutic to the target site with independent, sustainable release kinetics. To achieve that, we have designed and developed a set of disk-shaped microparticles composed of two distinct compartments, the first containing a relatively hydrophilic amorphous polymer, poly(lactide-co-glycolide) and the second composed entirely of hydrophobic semicrystalline polylactide. These bicompartmental microparticles with narrow particle size distribution (coefficient of variance ~ 6%) were fabricated by electrohydrodynamic co-jetting technique and characterized by optical microscopy, confocal laser scanning microscopy, SEM, DSC and Raman microscopy. The feasibility of the bicompartmentalized microparticles was confirmed by localizing two different hydrophilic PD drugs (LD and CD) in two different compartments with 4:1 ratio similar to commercially available tablets. This one-step particle fabrication method generated bicompartmental particles with high drug encapsulation efficiency (LD: > 97% and CD: > 68%). The resulting dual drug-loaded disk-shaped microparticles demonstrated simultaneous release of two independent PD drugs with similar release pattern (> 80% release of both drugs within 5 h). These compartmentalized microparticles can potentially act as dual drug delivery system to enable controlled, sustained release of a wide range of water soluble drugs including PD drugs.