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

The review consolidates preclinical evidence for intranasal NLC-CBD: in established animal models such as pentylenetetrazol-induced convulsions, the formulation increased brain CBD levels, facilitated anticonvulsant action, and protected against seizures. Relative to prior literature discussing oral CBD or nanocarriers separately, this work places NLC delivery, the intranasal route, and the specific DS/LGS indications within a single comparative frame. Evidence comes from preclinical animal-model studies (e.g., pentylenetetrazol-induced convulsions), representing mechanism and proof-of-concept rather than patient data.

The review reports that NLC-based preparations achieve higher brain-to-plasma ratios and longer central exposure at lower doses compared with free or orally administered CBD. This comparison links delivery-system differences directly to brain exposure and dose, supporting the rationale that intranasal administration may reduce systemic exposure and speed onset. Based on preclinical pharmacokinetic and brain-distribution comparisons; the text does not provide specific values or sample sizes.

The review identifies translational gaps from preclinical work to the clinic, including insufficient long-term safety data, lack of disease-specific DS/LGS genetic models, inconsistencies in pediatric nasal physiology, and conventional clinical dosing paradigms. It organizes translational barriers into safety, model, pediatric physiology, and dosing categories, offering a problem list for subsequent trial design. A review-level judgment based on the overall retrieved literature rather than a single experimental dataset.

The review proposes a path forward: properly designed clinical trials are needed to demonstrate the safety, pharmacokinetics, and efficacy of intranasal NLC-CBD in DS and LGS, and it mentions first pediatric clinical trials, adaptive trial models, regulatory harmonization, and future possibilities such as artificial intelligence, novel trial designs, and combination therapies. It specifies the trial and regulatory steps needed to translate the nanomedicine approach and lists technical directions worth exploring. Outlook and recommendations; the text does not report results from completed clinical trials.

The conclusions apply to the development context of intranasal NLC-CBD for the specific pediatric refractory epilepsy population of DS and LGS, with an evidence base of animal models and preclinical pharmacokinetic studies; what it can currently support is a research agenda and trial-design direction rather than clinical prescribing advice. For readers interested in nanodelivery, intranasal administration, or pediatric epilepsy trial design, the review offers an actionable list of translational questions.

Readers should still watch: whether long-term safety data are sufficient, whether DS/LGS-specific genetic models can be established, how pediatric nasal physiology differences affect dosing and exposure, and how conventional dosing paradigms should be adjusted. In addition, this reading was a summary-level fast parse lacking figures and specific values, so the magnitude of the brain-to-plasma ratios, doses, and exposure differences mentioned in the text cannot be confirmed here and would need to be checked against the original.