Effective Brain Targeting Using the Self-Emulsifying Drug Delivery Systems

The administration of neurotherapeutics is severely hindered by the blood-brain barrier (BBB), which limits drug transport to the brain. Self-emulsifying drug delivery systems (SEDDS) offer a promising nanocarrier strategy for improving the solubility, transmembrane permeability across the BBB, and targeted delivery of lipophilic drugs to the central nervous system. This review highlights the formulation principles, excipient selection, and mechanistic insights into SEDDS-mediated enhancement of BBB transport. A critical evaluation of the translational potential and pharmacokinetic benefits of both oral and intranasal SEDDS is presented, along with discussions on innovations in ligand-functionalized, hybrid, and mucoadhesive SEDDS. Additionally, the application of AI/ML-driven optimization tools for preformulation design, along with physiologically based pharmacokinetic (PBPK) modelling, is discussed, and a comparative analysis of reported SEDDS compositions with AI-based formulation predictions is presented. Clinical readiness is assessed through an overview of preclinical outcomes, the patent landscape, and emerging innovation trajectories. This review also addresses key challenges, including excipient safety, scale-up hurdles, and regulatory compliance, providing expert insights into future directions for the clinical translation and optimization of SEDDS for neurotherapeutic delivery.