Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI₅₀ values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism

Background: Cannabis sativa L. (C. sativa) has a long history of medicinal use. Its inflorescences contain bioactive compounds like non-psychotropic cannabidiol (CBD), which is well known for its anti-inflammatory potential in skin conditions such as psoriasis, and psychotropic Δ-9-tetrahydrocannabinol (THC). Keratinocytes, the main cells in the epidermis, are crucial for regulating skin inflammation by producing mediators like IL-8 when stimulated by agents like TNFα. Methods: This study explores the anti-inflammatory effects of a standardized C. sativa extract (CSE) with 5% CBD and less than 0.2% THC in human keratinocytes challenged by TNFα. The aim of this study is to analyze the specific contributions of the main constituents of CSE to inflammatory responses in human keratinocytes by fractionating the extract and examining the effects of its individual components. Results: MTT assays showed that CSE was non-toxic to HaCaT cells up to 50 μg/mL. CSE inhibited NF-κB activity and reduced IL-8 secretion in a concentration-dependent manner, with mean IC₅₀ values of 28.94 ± 10.40 μg/mL and 20.06 ± 2.78 μg/mL (mean ± SEM), respectively. Fractionation of CSE into four subfractions revealed that the more lipophilic fractions (A and B) were the most effective in inhibiting NF-κB, indicating that cannabinoids and cannflavins are key contributors. Pure CBD is one of the most active cannabinoids in reducing NF-κB-driven transcription (together with THC and cannabigerol), and due to its abundance in CSE, it is primarily responsible for the anti-inflammatory activity. Conclusions: This study highlights CBD’s significant role in reducing inflammation in human keratinocytes and underscores the need to consider the synergistic interactions of several molecules within C. sativa extracts for maximum efficacy. Standardized extracts are essential for reproducible results due to the variability in responses.

The preparation of 7R-HMR (allo-hydroxymatairesinol) is reported by: (a) NaBH₄ kinetic reduction of 7R/7S diastereomeric mixture; and (b) epimerization of the C7 hydroxyl group by Mitsunobu reaction and subsequent ester hydrolysis. The availability of highly pure target compound (7R-HMR) made it possible to confirm the structure of the target compound and to complete the full spectroscopic characterization.

Background/Objectives: Cannabigerol (CBG) is a non-psychoactive phytocannabinoid with significant therapeutic potential, showing emerging applications in drug delivery. This study aimed to develop and evaluate CBG-conjugated nanoparticles (NPs) incorporating tubulin-targeting drugs to enhance anticancer activity. Methods: CBG was conjugated with N-desacetylthiocolchicine, paclitaxel, and camptothecin using sebacic acid and 4,4′-dithiodibutyric acid as linkers, and nanoparticles were obtained. The NPs were characterized by their stability and size (hydrodynamic diameters < 90 nm). Their antiproliferative activity was assessed in three human tumor cell lines and non-tumorigenic cells. Their cellular uptake and mechanisms of action were investigated via confocal microscopy and cell cycle analysis. Results: The chemical composition of the linkers significantly influenced the antiproliferative effect, with the NPs containing 4,4′-dithiodibutyric acid demonstrating higher activity. Notably, NP3b, formulated with this linker, exhibited up to an 80-fold increase in antiproliferative potency compared to its sebacic acid counterpart (NP3a). In mesothelioma cells (MSTO-211H), NP3b displayed significantly higher cytotoxicity than in non-tumorigenic mesothelial cells (MeT-5A), indicating selectivity for cancer cells. Further analysis in glioblastoma cells confirmed that the NPs retained the microtubule-disrupting effects of their parent drugs. Conclusions: These findings highlight the potential of CBG-based NPs as versatile nanomedicine platforms for targeted cancer therapy. This study underscores the importance of linker chemistry in modulating therapeutic efficacy and supports the development of multifunctional drug delivery systems.