Intranasal nanocarrier-based drug delivery in multiple sclerosis: therapeutic cargo, CNS targeting and translational challenges

Efficiently delivering therapeutics to the central nervous system (CNS) remains a major challenge in multiple sclerosis (MS), particularly for strategies targeting CNS-resident pathology, neuroprotection, or remyelination. This review provides a delivery- and formulation-centered comparative analysis of CNS drug delivery strategies for MS, integrating administration route, nanocarrier design, evidence level, and translational feasibility within a unified framework. A structured narrative review was conducted using literature identified through PubMed, Scopus, and Google Scholar, encompassing conventional and alternative administration routes, including intranasal (IN) delivery, and lipid-based, polymeric, and hybrid nanocarrier systems. Strategies were evaluated using predefined criteria, including BBB permeability or CNS exposure, targeting capability, bioavailability, formulation characteristics, and translational feasibility. A semi-quantitative heatmap based on a predefined ordinal scoring system and available experimental and clinical evidence was developed to enable transparent comparison. Conventional systemic administration may be limited by systemic exposure, first-pass metabolism, and restricted CNS access. IN administration is a promising investigational approach to enhance CNS exposure for selected compounds; however, evidence for direct nose-to-brain (N2B) transport depends on the drug, formulation, and experimental model. Nanocarriers can improve solubility and stability, protect against degradation, enable controlled release, and may enhance CNS exposure or cellular targeting in selected preclinical settings. Nevertheless, evidence for BBB penetration, direct CNS targeting, and therapeutic efficacy remains predominantly preclinical, with limited standardized pharmacokinetic and clinical validation. Overall, the comparative framework highlights the importance of jointly considering administration route, nanocarrier properties, and evidence maturity to guide rational CNS delivery design and future translational development in MS.

Abstract from PubMed (PMID 43007498). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.