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Poly(ethylene glycol)-b-poly(epsilon-caprolactone) nanoparticles as a platform for the improved oral delivery of cannabidiol

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Abstract

Cannabidiol (CBD), a non-psychoactive constituent of Cannabis, has proven neuroprotective, anti-inflammatory and antioxidant properties though his therapeutic use, especially by the oral route, is still challenged by the poor aqueous solubility that results in low oral bioavailability. In this work, we investigate the encapsulation of CBD within nanoparticles of a highly hydrophobic poly(ethylene glycol)-b-poly(epsilon-caprolactone) block copolymer produced by a simple and reproducible nanoprecipitation method. The encapsulation efficiency is ~ 100% and the CBD loading 11% w/w (high performance liquid chromatography). CBD-loaded nanoparticles show a monomodal size distribution with sizes of up to 100 nm (dynamic light scattering), a spherical morphology, and the absence of CBD crystals (high resolution-scanning electron microscopy and cryogenic-transmission electron microscopy) which is in line with a very efficient nanoencapsulation. Then, the CBD release profile from the nanoparticles is assessed under gastric- and intestine-like conditions. At pH 1.2, only 10% of the payload is released after 1 h. Conversely, at pH 6.8, a release of 80% is recorded after 2 h. Finally, the oral pharmacokinetics is investigated in rats and compared to a free CBD suspension. CBD-loaded nanoparticles lead to a statistically significant ~ 20-fold increase of the maximum drug concentration in plasma (Cmax) and a shortening of the time to the Cmax (tmax) from 4 to 0.3 h, indicating a more complete and faster absorption than in free form. Moreover, the area-under-the-curve (AUC), a measure of oral bioavailability, increased by 14 times. Overall results highlight the promise of this simple, reproducible, and scalable nanotechnology strategy to improve the oral performance of CBD with respect to common oily formulations and/or lipid-based drug delivery systems associated with systemic adverse effects.

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Acknowledgements

A.S. thanks the support of the Tamara and Harry Handelsman Academic Chair. D.M. thanks Ohad Guberman for methodological support. I.S.L. thanks the Russell Berrie Nanotechnology Institute (RBNI, Technion – Israel Institute of Technology) for the doctoral scholarship.

Funding

This research was funded in part by the RBNI (Technion – Israel Institute of Technology).

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Authors and Affiliations

  1. Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion – Israel Institute of Technology, Technion City, Haifa, 320003, Israel

    Inbar Shreiber-Livne & Alejandro Sosnik

  2. Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion – Israel Institute of Technology, Haifa, 3200003, Israel

    Inbar Shreiber-Livne, Anna Shapira, Shiri Procaccia & David Meiri

  3. Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, 3200003, Israel

    Inbar Shreiber-Livne

  4. The Kleifeld Laboratory, Department of Biology, Technion – Israel Institute of Technology, Haifa, 3200003, Israel

    Liron Sulimani

  5. CannaSoul Analytics, Caesarea, 3099109, Israel

    Liron Sulimani

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  1. Inbar Shreiber-Livne
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  2. Liron Sulimani
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Contributions

Conceptualization: D.M, A.S; Methodology: I.S.L., L.S., A.Sh.; Data analysis: I.S.L., L.S., A.Sh.; Writing — original draft preparation, I.S., D.M., S.P., A.S.; supervision, D.M. and A.S.; funding acquisition: D.M. and A.S.; project administration, D.M. and A.S.

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Correspondence to David Meiri or Alejandro Sosnik.

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Shreiber-Livne, I., Sulimani, L., Shapira, A. et al. Poly(ethylene glycol)-b-poly(epsilon-caprolactone) nanoparticles as a platform for the improved oral delivery of cannabidiol. Drug Deliv. and Transl. Res. 13, 3192–3203 (2023). https://doi.org/10.1007/s13346-023-01380-1

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