Cannabidiol-Loaded Lipid-Stabilized Nanoparticles Alleviate Psoriasis Severity in Mice: A New Approach for Improved Topical Drug Delivery.

Cannabidiol (CBD) is a promising natural agent for treating psoriasis. CBD activity is attributed to inhibition of NF-kB, IL-1ß, IL-6, and IL-17A. The present study evaluated the anti-psoriatic effect of cannabidiol in lipid-stabilized nanoparticles (LSNs) using an imiquimod (IMQ)-induced psoriasis model in mice. CBD-loaded LSNs were stabilized with three types of lipids, Cetyl alcohol (CA), Lauric acid (LA), and stearic-lauric acids (SALA), and were examined in-vitro using rat skin and in-vivo using the IMQ-model. LSNs loaded with coumarin-6 showed a localized penetration depth of about 100 µm into rat skin. The LSNs were assessed by the IMQ model accompanied by visual (psoriasis area severity index; PASI), histological, and pro-psoriatic IL-17A evaluations. Groups treated with CBD-loaded LSNs were compared to groups treated with CBD-containing emulsion, unloaded LSNs, and clobetasol propionate, and to an untreated group. CBD-loaded LSNs significantly reduced PASI scoring compared to the CBD emulsion, the unloaded LSNs, and the untreated group (negative controls). In addition, SALA- and CA-containing nanoparticles significantly inhibited IL-17A release, showing a differential response: SALA > CA > LA. The data confirms the effectiveness of CBD in psoriasis therapy and underscores LSNs as a promising platform for delivering CBD to the skin.

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.