Amorphous Solid Dispersion Hydrogel Platform for Transdermal Delivery of Cannabidiol with Therapeutic Potential for...

Background/Objectives: Cannabis sativa is the source of cannabidiol (CBD), a non-intoxicating phytocannabinoid with analgesic and anti-inflammatory qualities that has demonstrated therapeutic potential in inflammatory skin conditions like dermatitis. However, low bioavailability and poor water solubility restrict its topical application. This study attempted to improve CBD solubility and transdermal delivery using an amorphous solid dispersion (ASD)-based hydrogel system. Methods: CBD was stabilized in its amorphous form using an ASD strategy and incorporated into a hydrogel matrix. The CBD-ASD hydrogel was characterized by particle size analysis, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR), rheological assessment, swelling studies, and diffusion experiments using Franz cells. Biological evaluations included cytotoxicity testing in human dermal fibroblast (HDF) cells, wound-healing assays, RT-qPCR-based anti-inflammatory analysis, antioxidant activity (DPPH assay), and antibacterial testing against Staphylococcus aureus. Results: Physicochemical analyses confirmed successful amorphous dispersion of CBD within a stable hydrogel network. The formulation exhibited sustained drug release over 144 h, achieving 86.32% cumulative release with diffusion-controlled kinetics. Rheological and swelling properties demonstrated mechanical stability and hydration suitability for long-term topical application, while Franz diffusion studies confirmed effective transdermal permeation. The CBD-ASD hydrogel showed no cytotoxicity in HDF cells and significantly enhanced wound closure. It also downregulated pro-inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Additionally, the formulation demonstrated 65.63 ± 10.00% DPPH radical scavenging activity and over 99% antibacterial inhibition. Conclusions: The CBD-ASD hydrogel represents a stable, multifunctional delivery platform that overcomes CBD solubility limitations and enhances therapeutic efficacy for inflammatory skin diseases.