Microneedle-mediated drug delivery for Parkinson's disease: advances, challenges, and future perspectives.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, affecting over 8.5 million individuals, with prevalence projected to exceed 12 million by 2040 due to global population aging. The escalating burden of PD presents substantial clinical and socioeconomic challenges, driven by progressive motor and non-motor dysfunctions that require lifelong pharmacotherapy. Current management remains suboptimal, as conventional oral therapies such as levodopa suffer from erratic gastrointestinal absorption, short plasma half-lives, extensive first-pass metabolism, and gut microbiota-mediated degradation, leading to fluctuating drug levels and motor complications. Although parenteral delivery can improve efficacy, its invasive nature limits long-term use. Microneedle-mediated drug delivery has emerged as a promising alternative, offering minimally invasive, patient-friendly administration while bypassing gastrointestinal and hepatic barriers. This review comprehensively evaluates microneedle technologies including solid, coated, dissolving, hydrogel-forming, and 3D-printed latticed systems for the delivery of levodopa, dopamine agonists, neuroprotective agents, and nanoparticle-based formulations in PD therapy. Emerging innovations such as stimuli-responsive microneedles, nano-enabled patches, and smart wearable microneedle-integrated sensors enable controlled drug release and real-time therapeutic monitoring. Preclinical studies consistently demonstrate enhanced dermal permeation, sustained pharmacokinetics, improved motor outcomes, and favorable biocompatibility. Despite remaining challenges in scalable manufacturing, regulatory standardization, and long-term clinical validation, microneedle-based systems represent a highly promising platform poised to transform future Parkinson's disease management.