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

Inbar Shreiber-Livne; Liron Sulimani; Anna Shapira; Shiri Procaccia; David Meiri; Alejandro Sosnik

doi:10.1007/s13346-023-01380-1

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

Drug Deliv Transl Res. 2023 Dec;13(12):3192-3203. doi: 10.1007/s13346-023-01380-1. Epub 2023 Jun 21.

Authors

Inbar Shreiber-Livne^{1

2

3}, Liron Sulimani^{4

5}, Anna Shapira², Shiri Procaccia², David Meiri⁶, Alejandro Sosnik⁷

Affiliations

¹ Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion - Israel Institute of Technology, Technion City, Haifa, 320003, Israel.
² Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
³ Russell Berrie Nanotechnology Institute, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
⁴ The Kleifeld Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel.
⁵ CannaSoul Analytics, Caesarea, 3099109, Israel.
⁶ Laboratory of Cancer Biology and Cannabinoid Research, Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel. dmeiri@technion.ac.il.
⁷ Laboratory of Pharmaceutical Nanomaterials Science, Department of Materials Science and Engineering, Technion - Israel Institute of Technology, Technion City, Haifa, 320003, Israel. sosnik@technion.ac.il.

PMID: 37341881
DOI: 10.1007/s13346-023-01380-1

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 (C_max) and a shortening of the time to the C_max (t_max) 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.

Keywords: Cannabidiol (CBD); Oral nano-drug delivery; Oral pharmacokinetics; Poly(epsilon-caprolactone); Polymeric nanoparticles.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cannabidiol*
Drug Carriers / chemistry
Nanoparticles* / chemistry
Polyesters / chemistry
Polyethylene Glycols / chemistry
Rats

Substances

Polyethylene Glycols
poly(epsilon-caprolactone)-b-poly(ethylene glycol)
Cannabidiol
Polyesters
Drug Carriers