Intranasal Conformal Patch for Sustained Levodopa Delivery and Reactive Oxygen Species Scavenging in Parkinson's Disease.

Abstract

Parkinson's disease (PD) imposes a heavy burden on the aging population. Current oral levodopa (LD) treatment faces dual challenges: poor brain bioavailability due to systemic barriers and motor complications from fluctuating drug levels. While intranasal delivery offers direct brain access, bypassing the blood-brain barrier, existing formulations still struggle to maintain stable drug concentrations needed to prevent motor fluctuations. Moreover, focusing solely on dopamine supplements overlooks the underlying oxidative stress that drives disease progression. Herein, we report an intranasal conformal patch composed of silk fibroin nanofibers that achieves stable drug delivery through moisture-responsive adhesion, sustained release, and enhanced LD stability. The patch further incorporates a dual-drug strategy combining LD supplementation with reactive oxygen species scavenging to delay neurodegeneration. <i>In vivo</i> results demonstrate that this daily patch effectively delivers nanomedicines to the brain, reverses pathological status, and restores normal behavioral patterns in PD models. This wearable drug reservoir enables sustained therapeutic effects while addressing oxidative damage, representing a significant advancement in PD treatment.