Cannabidiol-Loaded Nanoparticles Based on Crosslinked Starch: Anti-Inflammatory Activity and Improved Nose-to-Brain Delivery.

Cannabidiol (CBD) has previously been shown to inhibit inflammatory cytokine production in both in vitro and in vivo studies of neurodegenerative diseases. To date, the CBD treatment of these diseases by quantitative targeting directly to the brain is one of the greatest challenges. In this paper, we present a new particulate system capable of delivering CBD into the brain via the intranasal route. Intranasal administration of CBD-loaded starch nanoparticles resulted in higher levels of cannabidiol in the brain compared to an identically administered cannabidiol solution. The production and the characterization of starch-based nanoparticles was reported, as well as the evaluation of their penetration and anti-inflammatory activity in cells. Cannabidiol-loaded starch nanoparticles were prepared by crosslinking with divanillin, using the nanoprecipitation method. Evaluation of the anti-inflammatory activity in vitro was performed using the BV2 microglia cell line. The starch nanoparticles appeared under electron microscopy in clusters sized approximately 200 nm in diameter. In cultures of lipopolysaccharide-induced inflamed BV2 cells, the cannabidiol-loaded starch nanoparticles demonstrated low toxicity while effectively reducing nitric oxide production and IL-6 levels. The anti-inflammatory effect was comparable to that of a glucocorticoid. Starch-based nanoparticle formulations combined with intranasal administration may provide a suitable platform for efficacious cannabidiol delivery and activity in the central nervous system.

The Fundamental Role of Lipids in Polymeric Nanoparticles: Dermal Delivery and Anti-Inflammatory Activity of Cannabidiol.

This report presents a nanoparticulate platform for cannabidiol (CBD) for topical treatment of inflammatory conditions. We have previously shown that stabilizing lipids improve the encapsulation of CBD in ethyl cellulose nanoparticles. In this study, we examined CBD release, skin permeation, and the capability of lipid-stabilized nanoparticles (LSNs) to suppress the release of IL-6 and IL-8. The nanoparticles were stabilized with cetyl alcohol (CA), stearic acid (SA), lauric acid (LA), and an SA/LA eutectic combination (SALA). LSN size and concentration were measured and characterized by differential scanning calorimetry (DSC), in vitro release of loaded CBD, and skin permeability. IL-6 and IL-8 secretions from TNF-α-induced HaCaT cells were monitored following different LSN treatments. CBD released from the LSNs in dispersion at increasing concentrations of polysorbate 80 showed non-linear solubilization, which was explained by recurrent precipitation. A significant high release of CBD in a cell culture medium was shown from SALA-stabilized nanoparticles. Skin permeation was >30% lower from SA-stabilized nanoparticles compared to the other LSNs. Investigation of the CBD-loaded LSNs' effect on the release of IL-6 and IL-8 from TNF-α-induced HaCaT cells showed that nanoparticles stabilized with CA, LA, or SALA were similarly effective in suppressing cytokine release. The applicability of the CBD-loaded LSNs to treat topical inflammatory conditions has been supported by their dermal permeation and release inhibition of pro-inflammatory cytokines.

Characterization of nanoparticles made of ethyl cellulose and stabilizing lipids: Mode of manufacturing, size modulation, and study of their effect on keratinocytes.

We have developed an ethyl cellulose-based nanoparticulate system for encapsulation of sparingly soluble active pharmaceutical ingredients. Cannabidiol (CBD) and curcumin (CUR) were selected as model active ingredients. Using the nanoprecipitation method, nanoparticles ranged between 150 nm and 250 nm were obtained with an entrapment efficiency of >80%. It has been shown that incorporation of stabilizing lipids significantly reduced aggregation, increased the yield and the active ingredient-to-polymer ratio. In this study, we have explored the influence of process parameters on the extent of new particle core formation: chemical properties of the active ingredients, polymer concentrations, non-solvent addition rate, and the volume of the organic solvent for nanoparticle size control. The relationship between the particle radius [R] and the polymer concentration [Pol] was defined by R âˆ [Pol]n when n < ⅓. The extent of polymer supersaturation was related to the value of n, when the high polymer supersaturation increased the formation rate of new particle cores while decreasing polymer layering on the existing cores and the nanoparticles size. The obtained nanoparticles have shown low toxicity in keratinocytes, however, higher loadings of CUR or CBD resulted in increased toxicity. The nanoparticles effectively internalized into keratinocytes, implying their applicability for dermal delivery.