Lipid Nanoparticles versus Exosome-Based Systems for Central Nervous System Therapeutics: A Translational Perspective

Context: Central nervous system (CNS) therapeutics remain a defining challenge for nanomedicine because successful delivery requires nanocarriers to navigate a routedependent cascade of biological barriers, including systemic clearance, peripheral organ sequestration, blood-brain barrier (BBB) interaction or bypass, CNS tissue penetration, target-cell internalization, and functional payload availability.Purpose: This Perspective critically compares lipid nanoparticles (LNPs) and exosome-based systems as two leading non-viral nanocarrier platforms for CNS therapeutics.Rather than seeking a universal winner, we frame them as complementary delivery philosophies: engineering-led controllability for LNPs and biology-led functionality for exosome-based systems. Key arguments:We argue that CNS nanocarrier success must be defined by functional delivery rather than mere brain accumulation.LNPs offer scalable manufacturing, efficient nucleic acid encapsulation, tunable lipid chemistry, and clinical validation, but remain limited by peripheral clearance, restricted BBB penetration, and inefficient endosomal escape.Exosome-based systems offer endogenous communication pathways, membrane recognition, and biological interface functions, but their translation is hindered by source heterogeneity, difficult isolation and drug loading, batch inconsistency, endogenous cargo concerns, and regulatory ambiguity.Parkinson's Downloaded from https://www.cambridge.org/core.