Revolutionizing Neurological Therapies: The Multifaceted Potential of Zein-Based Nanoparticles for Brain-Targeted Drug Delivery.

Zein nanoparticles (ZNPs) have gained significant attention as biocompatible and biodegradable nanocarrier systems for brain-targeted drug delivery. Their ability to encapsulate hydrophobic drugs and undergo surface modifications enables effective blood-brain barrier (BBB) penetration through receptor-mediated transcytosis. Functionalization approaches, such as PEGylation and ligand conjugation, have been explored to enhance BBB transport and improve drug bioavailability. Additionally, ZNPs hold the potential for theranostic applications, integrating drug delivery with real-time diagnostics to facilitate personalized treatment strategies. This review provides a comprehensive evaluation of ZNPs, discussing their fabrication techniques, surface modifications, and transport mechanisms across the BBB. A comparative analysis with other nanocarrier systems (liposomes, polymeric NPs, dendrimers, lipid-based NPs, and carbon nanotubes) highlights their superior biodegradability, lower toxicity, and potential for clinical translation. Furthermore, we explore the latest advancements in ZNP-based drug delivery for neurological disorders, including glioblastoma, Parkinson's, and Alzheimer's. Despite their advantages, the clinical translation of ZNPs remains challenging due to scalability issues, batch-to-batch variability, and regulatory constraints. Future research should optimize functionalization strategies, enhance drug release kinetics, and conduct long-term safety evaluations. With continued advancements in nanotechnology and pharmaceutical engineering, ZNPs represent a promising, sustainable platform for improving brain-targeted therapeutic interventions.