Nanostructured lipid carriers for intranasal cannabidiol delivery in Dravet and Lennox-Gastaut syndromes: bridging preclinical promise to clinical translation.

Yashika S.; Yadav A.; Arora N.; Bharti A.; Kapil; Singh · Therapeutic delivery · 2026

**Background & Methods** This is a narrative review article examining nanostructured lipid carriers (NLCs) as a novel delivery system for cannabidiol (CBD) in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), two severe developmental epileptic encephalopathies with limited treatment options. The literature search covered PubMed, Scopus, Web of Science, and Google Scholar through March 2026, focusing on CBD, NLC technology, intranasal delivery, and these rare pediatric epilepsy syndromes. **Key Findings** • Intranasal NLC-CBD demonstrates preclinical evidence of increased brain CBD concentrations with faster anticonvulsant action and seizure protection in animal models (pentylenetetrazol-induced convulsions), achieving higher brain-to-plasma ratios and prolonged central nervous system exposure compared to free or orally administered CBD at lower doses. • Current oral CBD preparations are limited by low bioavailability, slow onset of action, and systemic adverse effects, whereas intranasal NLC delivery bypasses first-pass metabolism and gastrointestinal absorption, potentially enabling faster seizure control with reduced systemic exposure. • Multiple translational gaps remain unaddressed, including insufficient long-term safety data, lack of disease-specific genetic animal models for DS/LGS, inconsistencies in pediatric nasal physiology understanding, and need for pediatric-adapted clinical dosing paradigms before clinical translation. **Dosage & Administration** Not reported. The review emphasizes that intranasal NLC-CBD demonstrates capability for lower effective doses compared to oral formulations, but specific dosing recommendations are not provided. **Safety & Adverse Effects** Not reported. The review identifies insufficient long-term safety data as a critical translational gap but does not detail specific adverse effects from preclinical studies. **Evidence Quality** This is a narrative review article representing low-level evidence (Level 5). The analysis relies on preclinical animal data and existing literature rather than original clinical trials. Significant limitations include absence of human safety and efficacy data, lack of disease-specific genetic models, incomplete pediatric nasal physiology data, and unestablished clinical dosing protocols. The authors acknowledge the need for properly designed clinical trials, adaptive trial designs, regulatory harmonization, and pediatric-specific investigations before clinical implementation can be justified.

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