What question did this study set out to answer?

The aim is to improve drug delivery across the blood-brain barrier by functionalizing lipid nanocapsules with cannabidiol using click chemistry.

April 24, 2026Open Access

Improved drug delivery across the blood-brain barrier through post-insertion functionalization of lipid nanocapsules with cannabidiol using click chemistry

Key Points

The aim is to improve drug delivery across the blood-brain barrier by functionalizing lipid nanocapsules with cannabidiol using click chemistry.
Developing CBD-functionalized lipid nanocapsules (LNC1CBD and LNC2CBD) with varying sizes and functionalization efficiencies.
Conducting in vitro permeability assays and biodistribution studies in healthy mice to evaluate BBB translocation and brain accumulation.
Comparing performance of functionalized LNCs against non-functionalized counterparts in both healthy and diseased BBB models.
LNC2CBD shows a 55.77% increase in cellular uptake compared to non-functionalized LNCs.
LNC1CBD significantly enhances BBB permeability at earlier timepoints, while LNC2CBD performs better in later stages.
LNC1CBD and LNC2CBD achieve brain accumulation increases of 14.87% and 17.64%, respectively, within 30 minutes compared to non-functionalized LNCs.

Abstract

Crossing the blood-brain barrier (BBB) remains a major challenge in drug delivery for central nervous system (CNS) diseases. This study presents a covalent functionalization strategy to attach cannabidiol (CBD), the major non-psychotropic phytocannabinoid, to lipid nanocapsules (LNCs) to enhance their BBB permeability in vitro and in vivo . Using click chemistry, two highly monodisperse CBD-functionalized LNC formulations are prepared, LNC1CBD and LNC2CBD, with sizes of 27.0 ± 0.8 nm and 55.0 ± 2.5 nm, and functionalization efficiencies of 30.82 ± 5.93% and 29.59 ± 8.34%, respectively. LNC2CBD exhibits a 55.77% increase in cellular uptake relative to non-functionalized LNCs. In vitro permeability assays demonstrate that LNC1CBD significantly enhances translocation across the healthy BBB at earlier timepoints (4, 8 and 12 h), whereas LNC2CBD exhibits enhanced permeability at later stages (12 and 24 h) compared to their non-functionalized counterparts. This trend is maintained in a diseased BBB model, where CBD functionalization significantly improves permeability at nearly all timepoints for both formulations. Biodistribution studies in healthy mice validate these findings, revealing a consistent in vitro - in vivo correlation. LNC1CBD significantly increases brain accumulation by 14.87% at 30 minutes, while LNC2CBD maintains this effect, reaching 17.64% at 30 minutes, 38.23% at 90 minutes and 73.53% at 240 minutes, relative to non-functionalized LNCs. These findings underscore the potential of LNCs covalently functionalized with CBD as a promising platform for CNS-targeted delivery, which can ultimately open new avenues for therapeutic agents that do not usually reach the brain parenchyma at effective concentrations. • Cannabidiol (CBD) is covalently conjugated to lipid nanocapsules via click chemistry • Decoration with CBD enhances blood–brain barrier permeability in vitro and in vivo • Particle size critically influences brain accumulation of lipid nanocapsules • CBD-functionalized lipid nanocapsules represent a versatile platform for brain drug delivery

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Cite This Study

Pérez-López et al. (Wed,) studied this question.

synapsesocial.com/papers/69eb0899553a5433e34b3757 https://doi.org/https://doi.org/10.1016/j.colsurfb.2026.115736

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