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

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.