Therapeutic Polymer-Based Cannabidiol Formulation: Tackling Neuroinflammation Associated with Ischemic Events in the Brain

Abstract

Cannabidiol (CBD) is the most relevant nonpsychostimulant phytocompound found in Cannabis sativa. CBD has been extensively studied and has been proposed as a therapeutic candidate for neuroinflammation-related conditions. However, being a highly lipophilic drug, it has several drawbacks for pharmaceutical use, including low solubility and high permeability. Synthetic polymers can be used as drug delivery systems to improve CBD's stability, half-life, and biodistribution. Here, we propose using a synthetic polymer as a nanoparticulate vehicle for CBD (NPCBD) to overcome the pharmacological drawbacks of free drugs. We tested the NPCBDengineered system in the context of ischemic events in a relevant oxygen and glucose deprivation (OGD) model in primary cortical cells (PCC). Moreover, we have characterized the inflammatory response of relevant cell types, such as THP-1 (human monocytes), HMC3 (human microglia), and PCC, to NPCBD and observed a shift in the inflammatory state of the treated cells after the ischemic event. In addition, NPCBD exhibited a promising ability to restore mitochondrial function after OGD insult in both HMC3 and PCC cells at low doses of 1 and 0.2 μM CBD. Taken together, these results suggest the potential for preclinical use.

How Biodegradable Polymers Can be Effective Drug Delivery Systems for Cannabinoids? Prospectives and Challenges

“…NPs restored mitochondrial functions in Mito Stress assay. [ 236 ] Nanoparticles (NPs) CBD PLGA RG ® 502 236 ± 12 nm ζ = −16,6 ± 1.2 mV EE = 95.23 ± 3.30% In PBS pH 7.4: around 100% of the drug was released within 96h. SKOV-3 IC 50 = 29.64 ± 2.94 µM (after 24h) IC 50 = 20.88 ± 1.25 µM (after 48h) CAM (fertilized chicken eggs) SKOV-3 - About 80% tumor growth inhibition.…”

From bench to bedside: the application of cannabidiol in glioma

“…Many drugs fail to penetrate the BBB to any clinically meaningful extent, which is a crucial reason for the poor systemic treatment response in brain tumor patients [ 95 ]. The high lipophilicity of CBD presents challenges in drug bioavailability, distribution, and delivery: increased lipophilicity could potentially create a substrate for efflux pumps in the endothelial cells of BBB, negating the drug's entry through passive diffusion, and, similarly, heightened lipophilicity leads to reduced selectivity, augmented uptake in non-target tissues, increased tissue burden, and an expanded volume of distribution due to higher plasma protein binding rates [ 96 ]. Indeed, the nano-formulation of drugs offers enhanced bioavailability and targeting, allowing for reduced dosage and side effects, thereby decreasing the frequency of administration and increasing patient tolerance for treatment.…”