Dispersion of Cannabidiol Into Small-Sized Nanoparticles Using Technol PG

Abstract

Cannabidiol (CBD) has been used for the treatment of neuronal disease. Herein CBD was mixed with sodium cholate and Technol PG, a commercially available mixture of anionic phospholipids, which allowed for effective dispersion of the CBD in water.

Cannabidiol (CBD) (Figure 1A) is one of the cannabinoids contained in hemp plants. CBD has an affinity for cannabinoid receptors such as CB1 and CB2, ¹ and is known to be an antagonist of a G protein-conjugated receptor GPR55, which is thought to be a cannabinoid receptor expressed in the caudate nucleus and striatum. ² CBD has been frequently utilized for the treatment of neurological disorders, which span from anxiety, depression, and posttraumatic stress to neurodegenerative disorders, such as multiple sclerosis by regulating synaptic neurotransmission.^3–5 Despite these important pharmacological activities, the preclinical and clinical use of CBD remains difficult, due to its unfavorable characteristics, such as low solubility in aqueous media and important side effects. Indeed, for the administration to animals, CBD is sometimes dissolved in nonaqueous solvents or used as unstable suspensions. Thus, new formulation techniques solving the above problems would be useful for the development of novel CBD-based biomaterials. Lipid-based nanoparticles have been recently suggested as biodegradable and biocompatible nanocarriers for solubilization for the delivery of a large number of CBD molecules. ⁶ However, methods to disperse CBD into smaller-sized particles using more biocompatible and cheap phospholipids are still challenging.

Figure 1.

(A) Molecular structure of CBD, (B) molecular structure of PG and components of Technol PG, and (C) molecular structure of SC.

In this work, we utilized Technol PG for dispersing CBD into small-sized nanoparticles. Technol PG is cheaply provided by YOKOZEKI as compared with typical anionic phosphatidyl glycerol. Previously, we reported that mixtures of Technol PG (Figure 1B) and sodium cholate (SC) (Figure 1C) are useful for the creation of small-sized nanoparticles to encapsulate bioactive compounds. ⁷ As an extension of our studies, we found that the mixture of Technol PG and SC could also be used to disperse CBD. As a typical procedure for dispersing CBD, Technol PG powder (5.0 wt%), SC (2.0 wt%), and CBD (0.1 wt%) were mixed in water and ultrasonicated for 2 min. Without Technol PG and SC, a floating of CBD powder was observed (Figure 2B), but it turned into a transparent aqueous solution after mixing with Technol PG and SC (Figure 2C). Then, we evaluated the size of the particles by dynamic light scattering (DLS) analysis. Although bare CBD showed a peak around 1200 nm (Figure 2D), the size of the particles became smaller to 3 nm after being dispersed with Technol PG and SC (Figure 2E), confirming the creation of smaller CBD particles. It is noteworthy that such small-sized CBD nanoparticles using phospholipids have not been reported to our best knowledge. ⁶ Microscopic observation of the samples also revealed that bare CBD formed microparticles (Figure 3A) whereas CBD was dispersed into smaller CBD particles after the hybridization with Technol PG and SC (Figure 3B).

Figure 2.

(A) Synthetic illustrations for the preparation of CBD nanoparticles. Photograph of the dispersions of CBD (B) without and (C) with Technol PG (5.0 wt%) and SC (2.0 wt%). DLS profiles of the dispersions of CBD (0.1 wt%) (D) without and (E) with Technol PG (5.0 wt%) and SC (2.0 wt%).

Figure 3.

Microscopic observation of CBD (A) without and (B) with Technol PG (5.0 wt%) and SC (2.0 wt%). Scale bars: 20 μm.

In this study, we successfully dispersed CBD by mixing it with Technol PG and SC. CBD is known to be effective for treating anxiety, cognition, movement disorders, and pain. Technol PG-based CBD nanoparticles would be applicable as biomaterials for curing a variety of neuronal diseases after evaluating the biodistribution in the future.

Experimental

General: Technol PG was provided by YOKOZEKI. SC was purchased from TCI.

Preparation of CBD nanoparticles: For the preparation of CBD nanoparticles, Technol PG (5.0 wt%) and SC (2.0 wt%) were mixed with CBD (0.1 wt%) in water and ultrasonicated for 2 min.