Evaluations of Skin Permeability of Cannabidiol and Its Topical Formulations by Skin Membrane-Based Parallel Artificial Membrane Permeability Assay and Franz Cell Diffusion Assay

Abstract

<b><i>Introduction:</i></b> Cannabinoids including cannabidiol (CBD) have attracted enormous interest as bioactive ingredients for various dermatological and/or cosmeceutical uses. However, topical applications of cannabinoids might be limited without a fundamental understanding of their skin permeability. Herein, we aimed to evaluate the skin permeability of CBD and its topical formulations using artificial skin membrane assays. The solubility and stability of CBD in various surfactants that are commonly used in topical applications were also evaluated. <b><i>Methods:</i></b> CBD and two CBD-incorporated topical formulations (cream and gel) were prepared for this study. Computational predictions (SwissADME and DERMWIN™) and the parallel artificial membrane permeability assay (PAMPA) were used to evaluate the skin permeability of CBD isolate. The Franz cell diffusion (in vitro release testing) assay was used to evaluate the skin permeability of CBD formulations. The solubility and stability of CBD in surfactants were assessed by high-performance liquid chromatography and mass spectrometry analysis. <b><i>Results:</i></b> CBD isolate showed favorable skin permeability in the SwissADME and DERMWIN™ predictions (−Log Kp of 3.6 and 5.7 cm/s, respectively) and PAMPA (−LogPe value of 5.0 at pH of 6.5 and 7.4). In addition, CBD had higher solubility (378.4 μg/mL) in surfactant Tween 20 as compared to its solubility in polyisobutene. In an acidic environment (pH 5 and 6), Tween 20 maintained the CBD content at 81% and 70% over 30 days, respectively. CBD in the formulations of cream and gel also had moderate skin permeability in the Franz cell diffusion assay. <b><i>Conclusion:</i></b> Data from artificial membrane-based assays support that CBD is a skin permeable cannabinoid and the permeability and stability of its formulations may be influenced by several factors such as surfactant and pH environment. Findings from our study suggest that CBD may have suitable skin permeability for the development of dermatological and/or cosmeceutical applications but further studies using in vivo models are warranted to confirm this.

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

“…Our group reported that CBD can suppress the activation of the NLRP3 inflammasome in human monocytes via the regulation of the P2X7 receptor. 14 In addition, our study showed that CBD is skin permeable, 13 and it can protect human skin cells (keratinocytes) from hydrogen-peroxide-induced oxidative stress through the modulation of the caspase-1−IL-1β axis. 15 However, whether CBD can exert protective effects via the inhibition of ferroptosis in human skin cells remains unknown.…”

Stability, biofunctional, and antimicrobial characteristics of cannabidiol isolate for the design of topical formulations

“…This situation ensures minimal or no interaction between the active ingredient (e.g., CBD) and the other chemical ingredients in the formulation, such as waxes, surfactants (emulsifiers), oils, rheology modifiers, and water. 39 Thus, the most probable parameters that can affect the stability of CBD in the formulation are pH, temperature, as well as external environmental factors (frequency of light radiation, oxidation, humidity etc.) as previously mentioned in this section.…”

Exploring the Antibacterial Potential of Semisynthetic Phytocannabinoid: Tetrahydrocannabidiol (THCBD) as a Potential Antibacterial Agent against Sensitive and Resistant Strains of Staphylococcus aureus

“…In the Franz diffusion cell assay, THCBD ( 4 ) has shown good skin permeability (Figure ) and found that ∼4000 μg gets traversed over a period of 3 h and, during that time, THCBD ( 4 ) exhibits a steady-state flux of 254.32 μg·cm –2 ·h –1 . On the other hand, CBD ( 1 ) traversed only 47.6–51.8 μg over a time of 6–12 h in the Franz diffusion cell assay . THCBD ( 4 ) has shown a better permeability profile than CBD ( 1 ) and presents a suitable candidate for topical application.…”

“…On the other hand, CBD (1) traversed only 47.6−51.8 μg over a time of 6−12 h in the Franz diffusion cell assay. 58 THCBD (4) has shown a better permeability profile than CBD (1) and presents a suitable candidate for topical application.…”