Dissolvable Microneedles Embedded with Chitosan Nanoparticles for Transdermal Delivery of Pramipexole Dihydrochloride in Parkinson’s Disease

Abstract

Parkinson’s disease (PD), a progressive neurodegenerative disorder, presents significant challenges in long-term management due to the limitations of conventional oral dopaminergic therapy. Pramipexole dihydrochloride (Px), though clinically effective, is associated with gastrointestinal side effects and reduced compliance, especially in patients with dysphagia. To address these challenges, we developed a transdermal drug delivery system that integrates Px-loaded chitosan nanoparticles within dissolvable microneedle arrays. This hybrid platform combines the sustained release capability of polymeric nanoparticles with the minimally invasive administration of microneedles. The system is designed to penetrate the stratum corneum, dissolve upon insertion, and release Px nanoparticles for sustained dermal absorption. The microneedle arrays exhibit structural uniformity, mechanical robustness, and efficient skin insertion. The nanoparticles, in turn, enable controlled drug release while maintaining biocompatibility. Biological assessments confirmed the safety of the formulation, showing compatibility with human dermal cells and red blood cells. Moreover, ex vivo permeation studies demonstrated enhanced delivery of Px through human skin compared to free drug formulations. This work offers a promising solution for sustained, noninvasive delivery of dopaminergic therapy, with potential to improve clinical outcomes and quality of life in PD.