Next-Generation Phospholipid Nanocomplexes for Precision Neurotherapeutics: Harnessing Endogenous Blood-Brain Barrier Transport Mechanisms to Revolutionize the Treatment of Neurodegenerative Diseases

Abstract: The treatment of neurodegenerative illnesses remains a substantial problem due to the blood-brain barrier's restrictive nature, which restricts therapeutic agent penetration. Phospholipid Nanocomplexes (PNCs) have emerged as next-generation neurotherapeutics, utilizing natural BBB transport pathways to improve drug delivery. These nanocarriers, with lipid-based architectures, allow for receptor-mediated transcytosis, lipid raft-mediated transport, and adsorptive-mediated endocytosis, resulting in precise and sustained drug release inside the central nervous system. Recent preclinical and clinical studies have shown that PNC-based formulations of neurotrophic factors, antioxidants, and gene-silencing therapies significantly improve neuronal survival, cognitive function, and neuroprotection in conditions like Alzheimer's Disease (AD), Parkinson's Disease (PD), Glioblastoma (GBM), and multiple sclerosis. Despite the positive outcomes, issues such as scalability, long-term safety, and regulatory approval remain. This study critically assesses the present status of PNC-based neurotherapeutics, emphasizing their benefits over traditional therapies, analyzing the most recent clinical trial outcomes, and assessing difficulties and future prospects. To improve PNC effectiveness, the potential for artificial intelligence-driven medication design, multifunctionalized nanocarriers, and hybrid biomaterial methods is investigated. As biocompatible and patientspecific nanomedicine advances, PNCs represent a breakthrough approach to precision neuroscience, providing tailored, efficient, and safer therapies for neurodegenerative diseases.