Parkinson’s disease (PD) is still mainly treated with symptomatic therapies, while effective disease-modifying interventions remain limited. Although emerging therapeutics such as biologics, nucleic acid drugs, neurotrophic factors, and gene-based approaches offer new opportunities, their clinical translation is often restricted by inadequate brain delivery. Nanomedicine has therefore attracted increasing interest because it can improve drug stability, protect fragile cargos, enable controlled release, and support multifunctional therapeutic design. Nevertheless, the blood–brain barrier (BBB) remains the principal obstacle to effective brain-targeted therapy in PD. This review discusses nanomedicine-based delivery strategies for PD from the perspective of BBB navigation and classifies them into two major categories: strategies that cross the BBB and strategies that bypass it. BBB-crossing approaches include carrier-mediated transport, receptor-mediated transport, adsorptive and biomimetic transcytosis, and physically assisted methods such as focused ultrasound and photothermal modulation. BBB-bypassing approaches include intranasal delivery, meningeal lymphatic-associated pathways, skull–meninges-related microchannel routes, and local intracranial administration such as convection-enhanced delivery. We summarize their mechanisms, representative applications, advantages, and limitations, and compare them in terms of cargo suitability, delivery precision, repeatability, safety, and translational feasibility. Overall, nanomedicine provides important opportunities to expand the therapeutic potential of both conventional drugs and emerging biologics for PD. Future progress will depend on developing cargo-matched and clinically realistic delivery systems that balance brain access, therapeutic efficacy, safety, and manufacturability.
xiao et al. (Sun,) studied this question.
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