Enhancing cannabidiol bioaccessibility using ionic liquid as emulsifier to produce nanosystems: Characterization of structures, cytotoxicity assessment, and in vitro digestion.

The emulsifying potential of a biocompatible ionic liquid (IL) to produce lipid-based nanosystems developed to enhance the bioaccessibility of cannabidiol (CBD) was investigated. The IL (cholinium oleate) was evaluated at concentrations of 1 % and 2 % to produce nanoemulsions (NE-IL) and nanostructured lipid carriers (NLC-IL) loaded with CBD. The IL concentration of 1 % demonstrated to be sufficient to produce both NE-IL and NLC-IL with excellent stability properties, entrapment efficiency superior to 99 %, and CBD retention rate of 100 % during the storage period evaluated (i.e. 28 days at 25 °C). The in vitro digestion evaluation demonstrated that the NLC-IL provided a higher stability to the CBD, while the NE-IL improved the CBD bioaccessibility, which was mainly related to the composition of the lipid matrices used to obtain each nanosystem. Finally, it was observed that the CBD cytotoxicity was reduced when the compound was entrapped into both nanosystems.

Unraveling the Mechanisms of Cannabidiol's Pharmacological Actions: A Comprehensive Research Overview.

Cannabis sativa has long been used for neurological and psychological healing. Recently, cannabidiol (CBD) extracted from cannabis sativa has gained prominence in the medical field due to its non-psychotropic therapeutic effects on the central and peripheral nervous systems. CBD, also acting as a potent antioxidant, displays diverse clinical properties such as anticancer, antiinflammatory, antidepressant, antioxidant, antiemetic, anxiolytic, antiepileptic, and antipsychotic effects. In this review, we summarized the structural activity relationship of CBD with different receptors by both experimental and computational techniques and investigated the mechanism of interaction between related receptors and CBD. The discovery of structural activity relationship between CBD and target receptors would provide a direction to optimize the scaffold of CBD and its derivatives, which would give potential medical applications on CBD-based therapies in various illnesses.

Formulation Development and Evaluation of Cannabidiol Hot-Melt Extruded Solid Self-Emulsifying Drug Delivery System for Oral Applications.

Cannabidiol (CBD) is a highly lipophilic compound with poor oral bioavailability, due to poor aqueous solubility and extensive pre-systemic metabolism. The aim of this study was to explore the potential of employing Hot Melt Extrusion (HME) technology for the continuous production of Self Emulsifying Drug Delivery Systems (SEDDS) to improve the solubility and in vitro dissolution performance of CBD. Accordingly, different placebos were processed through HME in order to obtain a lead CBD loaded solid SEDDS. Two SEDDS were prepared with sesame oil, Poloxamer 188, Gelucire®59/14, PEO N80 and Soluplus®. Moreover, Vitamin E was added as an antioxidant. The SEDDS formulations demonstrated emulsification times of 9.19 and 9.30 min for F1 and F2 respectively. The formed emulsions showed smaller droplet size ranging from 150-400 nm that could improve lymphatic uptake of CBD and reduce first pass metabolism. Both formulations showed significantly faster in vitro dissolution rate (90% for F1 and 83% for F2) compared to 14% for the pure CBD within the first hour, giving an enhanced release profile. The formulations were tested for stability over a 60-day time period at 4°C, 25°C, and 40°C. Formulation F1 was stable over the 60-day time-period at 4°C. Therefore, the continuous HME technology could replace conventional methods for processing SEDDS and improve the oral delivery of CBD for better therapeutic outcomes.

Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo.

Purpose: Cannabidiol (CBD) is a promising therapeutic drug with low addictive potential and a favorable safety profile. However, CBD did face certain challenges, including poor solubility in water and low oral bioavailability. To harness the potential of CBD by combining it with a transdermal drug delivery system (TDDS). This innovative approach sought to develop a transdermal patch dosage form with micellar vesicular nanocarriers to enhance the bioavailability of CBD, leading to improved therapeutic outcomes. Methods: A skin-penetrating micellar vesicular nanocarriers, prepared using nano emulsion method, cannabidiol loaded transdermal nanocarriers-12 (CTD-12) was presented with a small particle size, high encapsulation efficiency, and a drug-loaded ratio for CBD. The skin permeation ability used Strat-M™ membrane with a transdermal diffusion system to evaluate the CTD and patch of CTD-12 (PCTD-12) within 24 hrs. PCTD-12 was used in a preliminary pharmacokinetic study in rats to demonstrate the potential of the developed transdermal nanocarrier drug patch for future applications. Results: In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application. Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation. Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application. Conclusion: CTD-12, a transdermal nanocarrier, represents a promising approach for CBD delivery, suggesting its potential as an effective transdermal dosage form.

Identification of Genes Hub Associated with Triple-Negative Breast Cancer and Cannabidiol Analogs Potential Inhibitory Agents: An In-silico Study.

OBJECTIVE: Triple-negative breast cancer presents a significant challenge in oncology due to its complex treatment and aggressive nature. This subtype lacks common cancer cell receptors like estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. This study aimed to identify, through bioinformatic analysis, the key genes associated with triple-negative breast cancer. In addition, CBD analogs with potential inhibitory effects on these genes were evaluated through docking and molecular dynamics. METHODS: Gene expression profiles from the GSE178748 dataset were analyzed, focusing on MDA-MB-231 breast cancer cell lines. Differentially expressed genes were determined through protein-protein interaction networks and subsequently validated. Additionally, the inhibitory effects of cannabidiol analogs on these hub genes were assessed using molecular docking and dynamics. RESULTS:  Analysis of the hub highlighted RPL7A, NHP2L1, and PSMD11 as significant players in TNBC regulation. Ligand 44409296 showed the best affinity energy with RPL7A, while 166505341 exhibited the highest affinity with NHP2L1 and PSMD11, surpassing CBD. Analyses of RMSD, RMSF, SASA, and Gyration Radius indicated structural stability and interactions of the proteins with ligands over time. MMGBSA calculations showed favorable binding energies for the ligands with the target proteins. CONCLUSION: In conclusion, this study identified key genes, namely RPL7A, NHP2L1, and PSMD11, associated with triple-negative breast cancer and demonstrated promising interactions with cannabidiol analogs, particularly 44409296 and 166505341. These findings suggest potential therapeutic targets and highlight the relevance of further clinical investigations. Additionally, the ligands exhibited favorable ADME properties and low toxicity, underscoring their potential in future drug development for TNBC treatment.

Development, Characterization and In Vitro Gastrointestinal Release of PLGA Nanoparticles Loaded with Full-Spectrum Cannabis Extracts.

Cannabinoids, such as ∆9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are effective bioactive compounds that improve the quality of life of patients with certain chronic conditions. The copolymer poly(lactic-co-glycolic acid) (PLGA) has been used to encapsulate such compounds separately, providing pharmaceutical grade edible products with unique features. In this work, a variety of PLGA based nanoformulations that maintain the natural cannabinoid profile found in the plant (known as full-spectrum) are proposed and evaluated. Three different cannabis sources were used, representing the three most relevant cannabis chemotypes. PLGA nanocapsules loaded with different amounts of cannabinoids were prepared by nanoemulsion, and were then functionalized with three of the most common coating polymers: pectin, alginate and chitosan. In order to evaluate the suitability of the proposed formulations, all the synthesized nanocapsules were characterized, and their cannabinoid content, size, zeta-potential, morphology and in vitro bioaccessibility was determined. Regardless of the employed cannabis source, its load and the functionalization, high cannabinoid content PLGA nanocapsules with suitable particle size and zeta-potential were obtained. Study of nanocapsules' morphology and in vitro release assays in gastro-intestinal media suggested that high cannabis source load may compromise the structure of nanocapsules and their release properties, and hence, the use of lower content of cannabis source is recommended.

The Inhibitory Effects of the Herbals Secondary Metabolites (7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol) on COVID-19: A Molecular Docking Study.

BACKGROUND: Since the COVID-19 outbreak in early 2020, researchers and studies are continuing to find drugs and/or vaccines against the disease. As shown before, medicinal plants can be very good sources against viruses because of their secondary compounds which may cure diseases and help in survival of patients. There is a growing trend in the filed patents in this field. AIMS: In the present study, we test and suggest the inhibitory potential of five herbal based extracts including 7α-acetoxyroyleanone, Curzerene, Incensole, Harmaline, and Cannabidiol with antivirus activity on the models of the significant antiviral targets for COVID-19 like spike glycoprotein, Papain-like protease (PLpro), non-structural protein 15 (NSP15), RNA-dependent RNA polymerase and core protease by molecular docking study. METHODS: The Salvia rythida root was extracted, dried, and pulverized by a milling machine. The aqueous phase and the dichloromethane phase of the root extractive were separated by two-phase extraction using a separatory funnel. The separation was performed using the column chromatography method. The model of the important antivirus drug target of COVID-19 was obtained from the Protein Data Bank (PDB) and modified. TO study the binding difference between the studied molecules, the docking study was performed. RESULTS: These herbal compounds are extracted from Salvia rhytidea, Curcuma zeodaria, Frankincense, Peganum harmala, and Cannabis herbs, respectively. The binding energies of all compounds on COVID-19 main targets are located in the limited area of 2.22-5.30 kcal/mol. This range of binding energies can support our hypothesis for the presence of the inhibitory effects of the secondary metabolites of mentioned structures on COVID-19. Generally, among the investigated herbal structures, Cannabidiol and 7α- acetoxyroyleanone compounds with the highest binding energy have the most inhibitory potential. The least inhibitory effects are related to the Curzerene and Incensole structures by the lowest binding affinity. CONCLUSION: The general arrangement of the basis of the potential barrier of binding energies is in the order below: Cannabidiol > 7α-acetoxyroyleanone > Harmaline> Incensole > Curzerene. Finally, the range of docking scores for investigated herbal compounds on the mentioned targets indicates that the probably inhibitory effects on these targets obey the following order: main protease> RNA-dependent RNA polymerase> PLpro> NSP15> spike glycoprotein.

Research Progress on the Mechanism of the Antitumor Effects of Cannabidiol.

Cannabidiol (CBD), a non-psychoactive ingredient extracted from the hemp plant, has shown therapeutic effects in a variety of diseases, including anxiety, nervous system disorders, inflammation, and tumors. CBD can exert its antitumor effect by regulating the cell cycle, inducing tumor cell apoptosis and autophagy, and inhibiting tumor cell invasion, migration, and angiogenesis. This article reviews the proposed antitumor mechanisms of CBD, aiming to provide references for the clinical treatment of tumor diseases and the rational use of CBD.

Nanosuspension-Loaded Dissolving Microneedle Patches for Enhanced Transdermal Delivery of a Highly Lipophilic Cannabidiol.

Purpose: Transdermal Drug Delivery System (TDDS) offers a promising alternative for delivering poorly soluble drugs, challenged by the stratum corneum's barrier effect, which restricts the pool of drug candidates suitable for TDDS. This study aims to establish a delivery platform specifically for highly lipophilic drugs requiring high doses (log P > 5, dose > 10 mg/kg/d), to improve their intradermal delivery and enhance solubility. Methods: Cannabidiol (CBD, log P = 5.91) served as the model drug. A CBD nanosuspension (CBD-NS) was prepared using a bottom-up method. The particle size, polydispersity index (PDI), zeta potential, and concentration of the CBD-NS were characterized. Subsequently, CBD-NS was incorporated into dissolving microneedles (DMNs) through a one-step manufacturing process. The intradermal dissolution abilities, physicochemical properties, mechanical strength, insertion depth, and release behavior of the DMNs were evaluated. Sprague-Dawley (SD) rats were utilized to assess the efficacy of the DMN patch in treating knee synovitis and to analyze its skin permeation kinetics and pharmacokinetic performance. Results: The CBD-NS, stabilized with Tween 80, exhibited a particle size of 166.83 ± 3.33 nm, a PDI of 0.21 ± 0.07, and a concentration of 46.11 ± 0.52 mg/mL. The DMN loaded with CBD-NS demonstrated favorable intradermal dissolution and mechanical properties. It effectively increased the delivery of CBD into the skin, extended the action's duration in vivo, and enhanced bioavailability. CBD-NS DMN exhibited superior therapeutic efficacy and safety in a rat model of knee synovitis, significantly inhibiting TNF-α and IL-1ß compared with the methotrexate subcutaneous injection method. Conclusion: NS technology effectively enhances the solubility of the poorly soluble drug CBD, while DMN facilitates penetration, extends the duration of action in vivo, and improves bioavailability. Furthermore, CBD has shown promising therapeutic outcomes in treating knee synovitis. This innovative drug delivery system is expected to offer a more efficient solution for the administration of highly lipophilic drugs akin to CBD, thereby facilitating high-dose administration.

Cannabidiol-Loaded Solid Lipid Nanoparticles Ameliorate the Inhibition of Proinflammatory Cytokines and Free Radicals in an In Vitro Inflammation-Induced Cell Model.

Cannabidiol (CBD) is a non-psychoactive compound derived from Cannabis sativa. It has demonstrated promising effects in combating inflammation and holds potential as a treatment for the progression of chronic inflammation. However, the clinical application of CBD is limited due to its poor solubility and bioavailability. This study introduces an effective method for preparing CBD-loaded solid lipid nanoparticles (CBD-SLNs) using a combination of low-energy hot homogenization and ultrasonication. We enhanced this process by employing statistical optimization with response surface methodology (RSM). The optimized CBD-SLN formulation utilizes glyceryl monostearate as the primary lipid component of the nanocarrier. The CBD-SLN formulation is screened as a potential tool for managing chronic inflammation. Stable, uniformly dispersed spherical nanoparticles with a size of 123 nm, a surface charge of -32.1 mV, an encapsulation efficiency of 95.16%, and a drug loading of 2.36% were obtained. The CBD-SLNs exhibited sustained release properties, ensuring prolonged and controlled CBD delivery, which could potentially amplify its therapeutic effects. Additionally, we observed that CBD-SLNs significantly reduced both reactive oxygen and nitrogen species and proinflammatory cytokines in chondrocyte and macrophage cell lines, with these inhibitory effects being more pronounced than those of free CBD. In conclusion, CBD-SLNs demonstrated superiority over free CBD, highlighting its potential as an effective delivery system for CBD.

Evaluation of amorphous and lipid-based formulation strategies to increase the in vivo cannabidiol bioavailability in piglets.

Cannabidiol (CBD) suffers from poor oral bioavailability due to poor aqueous solubility and high metabolism, and is generally administered in liquid lipid vehicles. Solid-state formulations of CBD have been developed, but their ability to increase the oral bioavailability has not yet been proven in vivo. Various approaches are investigated to increase this bioavailability. This study aimed to demonstrate the enhancement of the oral bioavailability of oral solid dosage forms of amorphous CBD and lipid-based CBD formulation compared to crystalline CBD. Six piglets received the three formulations, in a cross-over design. CBD and 7 - COOH - CBD, a secondary metabolite used as an indicator of hepatic degradation, were analyzed in plasma. A 10.9-fold and 6.8-fold increase in oral bioavailability was observed for the amorphous and lipid formulations, respectively. However, the lipid-based formulation allowed reducing the inter-variability when administered to fasted animals. An entero-hepatic cycle was confirmed for amorphous formulations. Finally, this study showed that the expected protective effect of lipids against hepatic degradation of the lipid-based formulation did not occur, since the ratio CBD/metabolite was higher than that of the amorphous one.

Formulation and In Vitro-Ex vivo Evaluation of Cannabidiol and Cannabidiol-Valine-Hemisuccinate Loaded Lipid-Based Nanoformulations for Ocular Applications.

The goal of this investigation is to develop stable ophthalmic nanoformulations containing cannabidiol (CBD) and its analog cannabidiol-valine-hemisuccinate (CBD-VHS) for improved ocular delivery. Two nanoformulations, nanoemulsion (NE) and nanomicelles (NMC), were developed and evaluated for physicochemical characteristics, drug-excipient compatibility, sterilization, thermal analysis, surface morphology, ex-vivo transcorneal permeation, corneal deposition, and stability. The saturation solubility studies revealed that among the surfactants tested, Cremophor EL had the highest solubilizing capacity for CBD (23.3 ± 0.1 mg/mL) and CBD-VHS (11.2 ± 0.2 mg/mL). The globule size for the lead CBD formulations (NE and NMC) ranged between 205 and 270 nm while CBD-VHS-NMC formulation had a particle size of about 78 nm. The sterilized formulations, except for CBD-VHS-NMC at 40 °C, were stable for three months of storage (last time point tested). Release, in terms of CBD, in the in-vitro release/diffusion studies over 18 h, were faster from the CBD-VHS nanomicelles (38 %) compared to that from the CBD nanoemulsion (16 %) and nanomicelles (33 %). Transcorneal permeation studies revealed improvement in CBD permeability and flux with both formulations; however, a greater improvement was observed with the NMC formulation compared to the NE formulation. In conclusion, the nanoformulations prepared could serve as efficient topical ocular drug delivery platforms for CBD and its analog.

Easy and Accessible Synthesis of Cannabinoids from CBD.

Cannabidiol (CBD), a prominent phytocannabinoid found in various Cannabis chemotypes, is under extensive investigation for its therapeutic potential. Moreover, because it is nonpsychoactive, it can also be utilized as a functional ingredient in foods and supplements in certain countries, depending on its legal status. From a chemical reactivity point of view, CBD can undergo conversion into different structurally related compounds both during storage and after the consumption of CBD-based products. The analytical determination of these compounds is of paramount concern due to potential toxicity and the risk of losing the active ingredient (CBD) title. Consequently, the complete stereoselective total synthesis of representative CBD-derived compounds has become a matter of great interest. The synthesis of pure CBD-derived compounds, achievable in a few synthetic steps, is essential for preparing analytical standards and facilitating biological studies. This paper details the transformation of the readily available CBD into Δ8-THC, Δ9-THC, Δ8-iso-THC, CBE, HCDN, CBDQ, Δ6-iso-CBD, and 1,8-cineol cannabinoid (CCB). The described protocols were executed without the extensive use of protecting groups, avoiding tedious purifications, and ensuring complete control over the structural features.

Development of Pure Certified Reference Material of Cannabidiol.

Cannabidiol (CBD) is the major functional component in hemp and has a broad range of pharmacological applications, such as analgesic, anti-epileptic, anti-anxiety, etc. Currently, CBD is widely used in pharmaceuticals, cosmetics, and food. To ensure the quality and safety of the products containing CBD, more and more related sample testing is being conducted, and the demand for CBD-certified reference material (CRM) has also sharply increased. However, there is currently a lack of relevant reference materials. In this paper, a simple method for preparing CBD CRM was established based on preparative liquid chromatography using crude hemp extract as a raw material. A qualitative analysis of CBD was performed using techniques such as ultraviolet absorption spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and differential scanning calorimetry (DSC). High-performance liquid chromatography (HPLC) was used for the homogeneity and stability tests, and the data were analyzed using an F-test and a T-test, respectively. Then, eight qualified laboratories were chosen for the determination of a certified value using HPLC. The results show that the CBD CRM had excellent homogeneity and good stability for 18 months. The certified value was 99.57%, with an expanded uncertainty of 0.24% (p = 0.95, k = 2). The developed CBD CRM can be used for the detection and quality control of cannabidiol products.

Exploring the Diverse Biological Properties of Cannabidiol: A Focus on Plant Growth Stimulation.

The aim of the current study was to compare some biological activities of edible oils enriched with 10 % of cannabidiol (CBD samples) from the Slovak market. In addition, hemp, coconut, argan, and pumpkin pure oils were also examined. The study evaluated the fatty acids content, as well as antibacterial, antifungal, antioxidant, cytotoxic, and phytotoxic activities. The CBD samples presented antimicrobial activity against the tested bacterial strains at higher concentrations (10000 and 5000 mg/L) and antifungal activity against Alternaria alternata, Penicillium italicum and Aspergillus flavus. DPPH⋅ and FRAP assays showed greater activity in CBD-supplemented samples compared to pure oils and vitamin E. In cell lines (IPEC-J2 and Caco-2), a reduced cell proliferation and viability were observed after 24 hours of incubation with CBD samples. The oils showed pro-germinative effects. The tested activities were linked to the presence of CBD in the oils.

In silico exploration of CB2 receptor agonist in the management of neuroinflammatory conditions by pharmacophore modeling.

Endocannabinoid system plays a pivotal role in controlling neuroinflammation, and modulating this system may not only aid in managing symptoms of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Multiple sclerosis, Epilepsy, Central and Peripheral neuropathic pain, but also, have the potential to target these diseases at an early-stage. In the present study, six different pharmacophore hypotheses were generated from Cannabidiol (CBD)-Cannabinoid Receptor subtype-2 (CB2) and then Zinc database was screened for identification of hit molecules. Identified 215 hit molecules were subjected to preliminary screening with ADMET and drug likeness properties, and about 48 molecules were found with no violations and toxicity properties. In molecular docking studies, six compounds showed better binding energy than CBD and ß-caryophyllene (known inhibitor of CB2). These six molecules were designated as leads and subjected to re-docking with glide tool and Lead1 (ZINC000078815430) showed docking score of -9.877 kcal/mol, whereas CBD and ß-caryophyllene showed score of -9.664 and -8.499 kcal/mol, respectively. Lead1 and CBD were evaluated for stability studies with Desmond tool by molecular dynamic simulation studies. Lead1 showed better stability than CBD in all studied parameters such as RMSD, RMSF, SSE, Rg, SASA, etc. In MM-GBSA free energy calculations, ΔGbinding energy of CB2-CBD complex and CB2-Lead1 were found to be -103.13±11.19 and -107.94±5.42 kcal/mol, respectively. Six lead molecules stated in the study hold promise with respect to CBD agonistic activity for treating and/or managing chronic conditions and can be explored as an alternative for early-stage cure, which has not yet been experimentally explored.

Phytochemical Characterization and TRPA1/TRPM8 Modulation Profile of the Cannabigerol-Rich Cannabis sativa L. Chemotype IV.

The first detailed phytochemical analysis of the cannabigerol (CBG)-rich chemotype IV of Cannabis sativa L. resulted in the isolation of the expected cannabigerolic acid/cannabigerol (CBGA/CBG) and cannabidiolic acid/cannabidiol (CBDA/CBD) and of nine new phytocannabinoids (5-13), which were fully characterized by HR-ESIMS and 1D and 2D NMR. These included mono- or dihydroxylated CBGA/CBG analogues, a congener with a truncated side chain (10), cyclocannabigerol B (11), and the CBD derivatives named cannabifuranols (12 and 13). Cyclocannabigerol B and cannabifuranols are characterized by a novel phytocannabinoid structural architecture. The isolated phytocannabinoids were assayed on the receptor channels TRPA1 and TRPM8, unveiling a potent dual TRPA1 agonist/TRPM8 antagonist profile for compounds 6, 7, and 14. Chiral separation of the two enantiomers of 5 resulted in the discovery of a synergistic effect of the two enantiomers on TRPA1.

Anti-Ferroptotic Effect of Cannabidiol in Human Skin Keratinocytes Characterized by Data-Independent Acquisition-Based Proteomics.

Skin cells are susceptible to oxidative stress and various types of cell death, including an iron-dependent form known as ferroptosis. Cannabidiol (CBD) can protect skin cells against oxidative stress, but whether this is attributed to the inhibition of ferroptosis is unknown. Herein, we evaluated the anti-ferroptotic effect of CBD in human keratinocytes using biochemical assays (radical scavenging and iron chelating) and cell-based models (for lipid peroxidation and intracellular iron). CBD's anti-ferroptotic effect was further characterized by proteomic analysis. This study identifies anti-ferroptosis as a mechanism of CBD's skin protective effects.

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug.

Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®.

Granite dust application to hemp - variety-specific impacts on growth and cannabinoid production.

The hemp industry has grown exponentially with the recent legalization of Cannabis sativa in Canada. With this new market expansion, there is an increased need for hemp plants, particularly for production of cannabinoids. Growing concerns regarding pesticide residues in commodities for human consumption, as well as global demand for fertilizer has increased consumer demand for natural products as alternatives to synthetic agrochemicals and pest management strategies. The objective of this study was to investigate the potential for using different composite granite dusts applied as soil amendments in improving C. sativa growth, and cannabinoid production (specifically, cannabidiol and cannabidiolic acid). We selected three varieties of industrial hemp with low yield production of cannabidiol (Fibranova, CFX-2, and Katani) and one variety with high yield production of cannabidiol (Cherry Blossom). Varieties were planted in potting soil amended with zero, five or ten percent granite dust mixture, and assayed for growth characteristics, and cannabinoid composition. Among tested cannabis varieties, results suggest that improvements to flower growth (> 44% mass) and cannabinoid production (> 2.5 fold or > 145%) from application of granite dust were evident in one variety of fibre hemp, CFX-2. Overall, this work suggests there may be selective benefits to soil applications of granite dust composites to improve hemp propagation, and that degree of improvement to cannabinoid production vary between varieties of hemp.