Multi-drug-loaded Microcapsules with Controlled Release for Management of Parkinson's Disease

Abstract

Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficient enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-L-lactide (PLLA) and poly (caprolactone) (PCL) were prepared through a modified double-emulsion technique. They were loaded with three PD drugs, i.e. levodopa (LD), carbidopa (CD) and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD were localized in both the hollow cavity and PLLA/PCL shell, while ENT was localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT was observed to be relatively slow as compared to the other hydrophilic drugs. It was further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibited similar release kinetics, according to Higuchi’s rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD.