Co-Dispersion Delivery Systems with Solubilizing Carriers Improving the Solubility and Permeability of Cannabinoids (Cannabidiol, Cannabidiolic Acid, and Cannabichromene) from Cannabis sativa (Henola Variety) Inflorescences

Abstract

Cannabinoids: cannabidiol (CBD), cannabidiolic acid (CBDA), and cannabichromene (CBC) are lipophilic compounds with limited water solubility, resulting in challenges related to their bioavailability and therapeutic efficacy upon oral administration. To overcome these limitations, we developed co-dispersion cannabinoid delivery systems with the biopolymer polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol (Soluplus) and magnesium aluminometasilicate (Neusilin US2) to improve solubility and permeability. Recognizing the potential therapeutic benefits arising from the entourage effect, we decided to work with an extract instead of isolated cannabinoids. Cannabis sativa inflorescences (Henola variety) with a confirming neuroprotective activity were subjected to dynamic supercritical CO2 (scCO2) extraction and next they were combined with carriers (1:1 mass ratio) to prepare the co-dispersion cannabinoid delivery systems (HiE). In vitro dissolution studies were conducted to evaluate the solubility of CBD, CBDA, and CBC in various media (pH 1.2, 6.8, fasted, and fed state simulated intestinal fluid). The HiE-Soluplus delivery systems consistently demonstrated the highest dissolution rate of cannabinoids. Additionally, HiE-Soluplus exhibited the highest permeability coefficients for cannabinoids in gastrointestinal tract conditions than it was during the permeability studies using model PAMPA GIT. All three cannabinoids exhibited promising blood-brain barrier (BBB) permeability (Papp higher than 4.0 × 10−6 cm/s), suggesting their potential to effectively cross into the central nervous system. The improved solubility and permeability of cannabinoids from the HiE-Soluplus delivery system hold promise for enhancement in their bioavailability.

Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems

“…The extraction process and preparation of the systems were performed as presented in our previous paper [71,72]. The extract from Cannabis sativa inflorescences was obtained by a dynamic supercritical CO 2 extraction process using the SFT-120 apparatus (shim-pol, Izabelin, Polska).…”

“…The cannabinoid profile (CBD, CBDA, and CBC) of the extract and the systems was analyzed using ultra-high-performance liquid chromatography with the diode array detector (HPLC-DAD)-validated method, Shimadzu Corp. (Kyoto, Japan). The previously described and validated method by the authors was used [35,71,72]. The mobile phase consisted of 0.1% trifluoroacetic acid and acetonitrile (41:59, v/v), and the column CORTECS Shield RP18 (2.7 µm; 150 mm × 4.6 mm, Cortecs, St. Paul, MN, USA) was used.…”

“…These systems have impacted stability and antimicrobial potential and offer implementation in food and personal care applications, such as sanitary materials or biomedical applications. Thus, current research studied the antimicrobial activity of Cannabis sativa systems known to increase solubility and apparent permeability after oral administration, aiming to impact the bioavailability and efficacy of cannabis constituents as it was shown in our previous article [71]. Cannabis sativa extract, Henola variety, has demonstrated neuroprotective activity in our earlier studies [71,72].…”

“…Thus, current research studied the antimicrobial activity of Cannabis sativa systems known to increase solubility and apparent permeability after oral administration, aiming to impact the bioavailability and efficacy of cannabis constituents as it was shown in our previous article [71]. Cannabis sativa extract, Henola variety, has demonstrated neuroprotective activity in our earlier studies [71,72]. The gut-brain axis, along with interactions with gut microbiota, significantly influences neuroprotective effects [73].…”

The Antioxidant and Neuroprotective Potential of Leaves and Inflorescences Extracts of Selected Hemp Varieties Obtained with scCO2

“…A linear regression equation was established to relate the trolox concentration with its corresponding scavenging percentage (DPPH and ABTS) or absorbance (CUPRAC and FRAP), subsequently, the results presented as mg trolox/g plant material were calculated through the equation, according to the antioxidant properties of the extracts in all four assays [43,44]. The antioxidant potential was determined according to the previously reported method [45,46]. Each measurement in the antioxidant studies was repeated six times.…”