Academic Journal
Improved drug delivery across the blood-brain barrier through post-insertion functionalization of lipid nanocapsules with cannabidiol using click chemistry.
| Τίτλος: | Improved drug delivery across the blood-brain barrier through post-insertion functionalization of lipid nanocapsules with cannabidiol using click chemistry. |
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| Συγγραφείς: | Pérez-López A; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, Madrid 28040, Spain., Aparicio-Blanco J; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, Madrid 28040, Spain; Institute of Industrial Pharmacy, Complutense University of Madrid, Madrid, Spain. Electronic address: juan.aparicio.blanco@ucm.es., Martín-Sabroso C; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, Madrid 28040, Spain; Institute of Industrial Pharmacy, Complutense University of Madrid, Madrid, Spain., Martins C; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal., Gómez-Lázaro L; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, Madrid 28040, Spain., Sebastián V; Department of Chemical and Environmental Engineering, Universidad de Zaragoza Campus Rio Ebro, Zaragoza 50018, Spain; Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza 50009, Spain; Laboratorio de Microscopías Avanzadas, Universidad de Zaragoza, Zaragoza 50018, Spain; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid 28029, Spain., González-Matilla JF; Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, Madrid 28040, Spain., Sarmento B; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal; INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal; IUCS-CESPU - InstitutoUniversitário de Ciências da Saúde, Rua Central de Gandra 1317, Gandra 4585-116, Portugal., Torres-Suárez AI; Department of Pharmaceutics and Food Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal, Madrid 28040, Spain; Institute of Industrial Pharmacy, Complutense University of Madrid, Madrid, Spain. |
| Πηγή: | Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2026 Sep; Vol. 265, pp. 115736. Date of Electronic Publication: 2026 Apr 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9315133 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4367 (Electronic) Linking ISSN: 09277765 NLM ISO Abbreviation: Colloids Surf B Biointerfaces Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam ; New York : Elsevier, c1993- |
| Ιατρικοί όροι (MeSH): | Blood-Brain Barrier*/metabolism , Blood-Brain Barrier*/drug effects , Nanocapsules*/chemistry , Cannabidiol*/chemistry , Cannabidiol*/pharmacokinetics , Lipids*/chemistry , Click Chemistry* , Drug Delivery Systems*, Animals ; Mice ; Humans ; Particle Size ; Permeability |
| Περίληψη: | 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. LNC1CBD significantly increases brain accumulation by 14.87% at 30 min, while LNC2CBD maintains this effect, reaching 17.64% at 30 min, 38.23% at 90 min and 73.53% at 240 min, 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. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: CNS drug delivery; Cannabidiol; Click chemistry; In vitro BBB permeability; Lipid nanocapsules |
| Substance Nomenclature: | 0 (Nanocapsules) 19GBJ60SN5 (Cannabidiol) 0 (Lipids) |
| Entry Date(s): | Date Created: 20260426 Date Completed: 20260610 Latest Revision: 20260610 |
| Update Code: | 20260611 |
| DOI: | 10.1016/j.colsurfb.2026.115736 |
| PMID: | 42035499 |
| Βάση Δεδομένων: | MEDLINE |
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