Next-generation lipid nanocarriers for Parkinson's therapy: nose-to-brain innovations and clinical prospects

Parkinson's disease (PD) remains one of the most formidable challenges in central nervous system (CNS) drug delivery due to the restrictive blood-brain barrier (BBB) and limited efficacy of current dopaminergic therapies. Lipid-based nanocarriers, including liposomes, cubosomes, and nanostructured lipid carriers, have emerged as versatile nose-to-brain platforms offering rapid CNS access, dual encapsulation of synthetic and plant-derived neuroprotective agents, and tunable release kinetics. This review bridges nanoscale material design (e.g., lipid crystallinity, phase transitions, hybridization with plant exosomes) with intranasal transport pathways and therapeutic outcomes in PD. We highlight multifunctional innovations such as stimuli-responsive lipid systems, exosome-cubosome hybrids, and AI-guided formulation modeling coupled with microfluidic manufacturing. By linking mechanistic insights with translational hurdles-including safety and regulatory challenges-we provide a forward-looking roadmap for next-generation nanotherapies poised to redefine PD management and accelerate clinical translation.