Mucus-Penetrating Nanostructured Lipid Carriers: An Effective Approach for Cannabidiol to Pass Across the Nasal Mucus-Mucosal Barrier.

Wang L.; Liu B.; Luo Q.; Liang K.; Wang W.; Yang L.; Wang Q. · Journal of biomedical materials research. Part A · 2026

**Background & Methods** This review study evaluated nanostructured lipid carriers (NLCs) as a delivery system for cannabidiol (CBD) across the nasal mucus-mucosal barrier to facilitate nose-to-brain drug delivery. The research combined molecular docking simulations to assess mucin-NLC interactions, in vitro mucus penetration experiments, and cellular studies using rat nasal mucosal epithelial (RNME) cells to examine uptake, localization, and transport mechanisms of CBD-NLCs. **Key Findings** • Molecular docking simulations demonstrated minimal interactions between NLC components and human mucin protein (hMUC5AC), with in vitro experiments confirming that NLCs effectively penetrated the mucus layer with little mucin binding, suggesting reduced barrier impedance compared to conventional formulations. • Cellular uptake studies showed cytoplasmic (non-nuclear) localization of coumarin-6-labeled NLCs in RNME cells, with clathrin-mediated endocytosis identified as the predominant internalization pathway through confocal microscopy and endocytosis inhibition assays. • NLCs significantly enhanced transcellular transport of CBD across RNME cell monolayers, demonstrating superior permeation capabilities that support nose-to-brain delivery potential through the nasal epithelial barrier. **Dosage & Administration** Not reported. **Safety & Adverse Effects** Not reported. **Evidence Quality** This is a review article combining computational modeling and in vitro experimental data without clinical trials or in vivo animal studies. Major limitations include reliance on molecular docking simulations and isolated cell culture models, which may not fully replicate the complex in vivo nasal environment. The study uses rat epithelial cells rather than human tissues, limiting direct clinical translatability. No human safety data, pharmacokinetic profiles, or comparative efficacy data versus other delivery systems are provided. The lack of in vivo validation in animal models represents a significant gap before clinical application can be considered. As a preliminary mechanistic review, this provides moderate evidence supporting further investigation but insufficient evidence for clinical recommendation.

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