THC-Reduced Cannabis sativa L.-How Does the Solvent Determine the Bioavailability of Cannabinoids Given Orally?

The bioavailability levels of cannabidiol (CBD) and tetrahydrocannabinol (THC) determine their pharmacological effects. Therefore, for medical purposes, it is essential to obtain extracts containing the lowest possible content of the psychogenic component THC. In our extract, the CBD/THC ratio was 16:1, which is a high level compared to available medical preparations, where it is, on average, 1:1. This study assessed the bioavailability and stability of CBD and THC derived from Cannabis sativa L. with reduced THC content. The extract was orally administered (30 mg/kg) in two solvents, Rapae oleum and Cremophor, to forty-eight Wistar rats. The whole-blood and brain concentrations of CBD and THC were measured using liquid chromatography coupled with mass spectrometry detection. Much higher concentrations of CBD than THC were observed for both solvents in the whole-blood and brain after oral administration of the Cannabis sativa extract with a decreased THC content. The total bioavailability of both CBD and THC was higher for Rapae oleum compared to Cremophor. Some of the CBD was converted into THC in the body, which should be considered when using Cannabis sativa for medical purposes. The THC-reduced hemp extract in this study is a promising candidate for medical applications.

Scaffolds for drug delivery and tissue engineering: The role of genetics.

Scaffolds are implants commonly used to deliver cells, drugs, and genes into the body. Their regular porous structure ensures the proper support for cell attachment, proliferation, differentiated function, and migration. Techniques to fabricate a scaffold include leaching, freeze-drying, supercritical fluid technology, thermally induced phase separation, rapid prototyping, powder compaction, sol-gel, and melt molding. Gene delivery from the scaffold represents a versatile approach to influence the environment for managing cell function. Scaffolds can be used for various tissue engineering purposes, e.g. bone formation, periodontal regeneration, cartilage development, artificial corneas, heart valves, tendon repair, or ligament replacement. Moreover, they are also instrumental in cancer therapy, inflammation, diabetes, heart disease, and wound dressings. Scaffolds provide a platform to extend the delivery of drugs and genetic materials at a controlled timeframe, besides potentially being used to prevent infection upon surgery and other chronic diseases, provided that they can be formulated with specific medicines. This review discusses the need to design advanced functional scaffolds with the potential for modified drug delivery and tissue engineering in a synergistic approach. Special attention is given to works published in 2023 to generate the bibliometric map.

Tocilizumab-coated solid lipid nanoparticles loaded with cannabidiol as a novel drug delivery strategy for treating COVID-19: A review.

Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflammatory responses in COVID-19 patients. TCZ, as an immunosuppressive drug, is mainly used to treat rheumatoid arthritis, although several attempts have been made to use it in the active hyperinflammatory phase of COVID-19, with promising outcomes. TCZ is currently administered intravenously. It this review, we discuss the potential advances on the use of SLN for oral administration of TCZ-tailored CBD-loaded SLN, as an innovative platform for managing SARS-CoV-2 and related infections.

Phytocannabinoids: Chromatographic Screening of Cannabinoids and Loading into Lipid Nanoparticles.

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) are receiving increasing interest as an approach to encapsulate natural extracts to increase the physicochemical stability of bioactives. Cannabis extract-derived cannabidiol (CBD) has potent therapeutic properties, including anti-inflammatory, antioxidant, and neuroprotective properties. In this work, physicochemical characterization was carried out after producing Compritol-based nanoparticles (cSLN or cNLC) loaded with CBD. Then, the determination of the encapsulation efficiency (EE), loading capacity (LC), particle size (Z-Ave), polydispersity index (PDI), and zeta potential were performed. Additionally, the viscoelastic profiles and differential scanning calorimetry (DSC) patterns were recorded. As a result, CBD-loaded SLN showed a mean particle size of 217.2 ± 6.5 nm, PDI of 0.273 ± 0.023, and EE of about 74%, while CBD-loaded NLC showed Z-Ave of 158.3 ± 6.6 nm, PDI of 0.325 ± 0.016, and EE of about 70%. The rheological analysis showed that the loss modulus for both lipid nanoparticle formulations was higher than the storage modulus over the applied frequency range of 10 Hz, demonstrating that they are more elastic than viscous. The crystallinity profiles of both CBD-cSLN (90.41%) and CBD-cNLC (40.18%) were determined. It may justify the obtained encapsulation parameters while corroborating the liquid-like character demonstrated in the rheological analysis. Scanning electron microscopy (SEM) study confirmed the morphology and shape of the developed nanoparticles. The work has proven that the solid nature and morphology of cSLN/cNLC strengthen these particles' potential to modify the CBD delivery profile for several biomedical applications.

Simple Extraction of Cannabinoids from Female Inflorescences of Hemp (Cannabis sativa L.).

The high interest in non-psychoactive cannabidiol increases the need for efficient and straightforward cannabidiol (CBD) extraction methods. The research aimed to compare simple methods of cannabinoid extraction that do not require advanced laboratory equipment. This work assesses the content of total CBD and Δ9-tetrahydrocannabinol (Δ9-THC) in popular solvents such as water and ethanol extracts. Hemp raw material was analyzed with Gas Chromatography with a Flame Ionization Detector (GC-FID), while extracts were tested by High-Performance Liquid Chromatography (HPLC). The female inflorescences of three varieties of industrial hemp were tested: Futura 75, KC Dora, and Tygra (different sowing and N fertilization densities). Tygra (T/10/30) showed the highest content of CBD (0.064%) in water extracts. However, in 80% tincture from Futura 75 (F/30/30), a higher CBD content of 1.393% was observed. The use of 96% ethanol for extraction and ultrasound enabled the highest CBD content to be obtained: 2.682% in Futura 75 (F/30/30). Cold water extraction showed no effect on Δ9-THC content, while hot water extraction increased content from 0.001% in KC Dora to 0.002% in Futura 75 (F/30/30) and Tygra, but the changes were statistically insignificant. Application of 80% ethanol revealed the significantly highest content of Δ9-THC in KC Dora, from 0.026% (K/30/90) to 0.057% (K/30/30), as well as in Tygra (T/30/30) (0.036%) and Futura 75 (F/30/30) (0.048%). The use of ethanol extraction in combination with ultrasound could be an efficient method of obtaining cannabinoids.