Transdermal delivery of pramipexole dihydrochloride using dissolving polymeric microneedle patches for improved Parkinson's disease management

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder commonly treated with oral pramipexole dihydrochloride monohydrate (PXCl), a dopamine agonist. Oral therapy is often limited by gastrointestinal complications, variable absorption, and poor patient adherence, highlighting the need for alternative delivery strategies. Dissolving microneedles (MNs) offer a minimally invasive, patient-friendly platform for transdermal drug delivery, enabling sustained and controlled release. In this study, PXCl-loaded MNs were developed using three polymer blends: polymethyl-vinyl-ether- co -maleic acid/polyvinyl alcohol (PMVEMA-PVA30K), carboxymethylcellulose sodium/polyvinyl alcohol (CMC-PVA30K), and polyvinylpyrrolidone/polyvinyl alcohol (PVP-PVA70K). Micro-molding produced MNs with sharp, uniform geometries, and adequate mechanical strength to penetrate the skin, achieving insertion efficiencies above 94%. Fourier-transform infrared spectroscopy confirmed intermolecular hydrogen bonding and ionic interactions between PXCl and the polymer matrices. In vitro release studies across cellulose membranes demonstrated complete PXCl release within 48–72 h, with faster release from CMC- and PVP-based MNs. Notably, PMVEMA-PVA30K MNs, despite slower release, showed the highest PXCl permeation and flux across full-thickness human skin, likely due to stronger drug-polymer interactions, enhanced MN rigidity, and polymer-induced modulation of skin permeability. Biocompatibility assays indicated that all formulations were non-hemolytic and non-cytotoxic. These findings demonstrate that dissolving MNs provide a promising strategy for transdermal PXCl delivery and suggest that PMVEMA-PVA30K matrices may offer an effective, sustained therapeutic approach for PD treatment.