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Enhancing transmucosal delivery of CBD through nanoemulsion: in vitro and in vivo studies

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Abstract

Cannabidiol (CBD) has gained significant attention as a complementary and alternative medicine due to its promising therapeutic properties. However, CBD faces obstacles when administered orally due to its poor solubility in water, leading to limited absorption into the bloodstream and low and variable bioavailability. Therefore, the development of innovative delivery approaches that can enhance CBD’s bioavailability, facilitate administration, and promote patient adherence is crucial. We propose a new approach for buccal delivery of CBD based on a self-assembling nanoemulsion (NE) made of a mixture of surfactants (Tween 80 and Labrasol) and medium chain triglycerides (MCTs). The NE formulation showed properties suitable for buccal administration, including appropriate size, CBD content, and surface properties, and, if compared to a CBD-MCT solution, it exhibited better control of administered doses, faster dissolution in buccal medium, and enhanced stability. The CBD-NE effectively released its active load within 5 h, remained stable even when diluted in simulated buccal fluids, and could be easily administered through a commercially available spray, providing consistent and reproducible doses of NE with optimized properties. In vitro permeation studies demonstrated that the CBD-NE facilitated swift and consistent permeation through the buccal mucosa, resulting in a higher concentration in the acceptor compartment compared to CBD-MCT. Furthermore, the in vivo study in mice showed that a single buccal administration of CBD-NE led to a quicker onset of action than a CBD solution in MCT, while maintaining the same plasma levels over time and leading to typically higher plasma concentrations compared to those usually achieved through oral administration. In conclusion, our CBD-NE represents a promising alternative formulation strategy for buccal CBD administration, overcoming the challenges associated with conventional formulations such as variable bioavailability and low control of administered doses.

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Data availability

The data that support the findings of this study are not openly available and are available from the corresponding author upon reasonable request.

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Acknowledgements

In loving memory of Professor Alberto Ritieni, who left us prematurely and suddenly. May his memory continue to inspire and guide future generations of researchers in their pursuit of knowledge and innovation.

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The authors declare that no funds, grants, or other support were received for the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Pharmacy, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy

    Romina Provenzano, Antonella Vitiello, Luana Izzo, Alberto Ritieni, Francesca Ungaro, Fabiana Quaglia & Agnese Miro

  2. Department of Science of Health, Magna Græcia University, Catanzaro, Italy

    Carmen De Caro & Emilio Russo

  3. DiSTABiF, University of Campania “Luigi Vanvitelli”, Via A. Vivaldi, 43, 81100, Caserta, Italy

    Ivana d’Angelo

Authors
  1. Romina Provenzano
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Contributions

Conceptualization, A.M., I.d., and F.Q.; methodology, I.d., F.U., A.R., and E.R.; formal analysis, A.M. and I.d.; investigation, R.P., A.V., C.D., and L.I.; resources, A.M., I.d., and E.R.; data curation, I.d., R.P., and E.R.; writing—original draft preparation, I.d.; writing—review and editing, I.d., F.Q., and A.M.; supervision and project administration, I.d. and A.M. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Agnese Miro.

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Ethics approval and consent to participate

Animal care and manipulations were conducted in conformity with international and national law and policies (EU Directive 2010/63/EU for animal experiments, ARRIVE guidelines, and the Basel declaration including the 3R concept). The procedure reported here was approved by the Institutional Committee on the Ethics of Animal Experiments (CVS) of the University Magna Graecia of Catanzaro and by Ministero della Salute (authorization no. 177/2019-PR).

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Provenzano, R., De Caro, C., Vitiello, A. et al. Enhancing transmucosal delivery of CBD through nanoemulsion: in vitro and in vivo studies. Drug Deliv. and Transl. Res. 14, 1648–1659 (2024). https://doi.org/10.1007/s13346-023-01481-x

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