Cannabidiol-Loaded Mucoadhesive PLGA Nanosphere-Chitosan Hydrogel Patch for Oral Therapeutic Applications

Cannabidiol (CBD), the primary bioactive element of cannabis, has shown promise in alleviating pain and inflammation, although mechanisms in periodontal inflammation are not fully understood. To improve its limited solubility and mucosal permeability, the developed chitosan-based mucoadhesive hydrogel incorporating CBD-loaded PLGA nanospheres (CPN hydrogel) was characterized by FT-IR, SEM, particle size, rheological, swelling, and diffusion analyses, followed by biological evaluations, including wound-healing and RT-qPCR-based anti-inflammatory assays. The improved CPN hydrogel had a homogeneous shape, better viscoelastic behavior, and sustained drug release. Over 90% of CBD was released within 96 h, and Franz cell experiments showed improved permeability (124.1 μg/cm² after 72 h). The gellan gum-based mucosal substrate significantly increased adhesion (1137.33 ± 142.25 s) compared to the control groups. Antioxidant studies indicated 73.65% DPPH radical scavenging, whereas antibacterial tests showed more than 99% suppression of <i>Staphylococcus aureus</i>. Furthermore, in vitro studies validated its wound healing and the downregulation of the inflammatory cytokines IL-6 and TNF-α. The results indicate that the CPN-loaded chitosan hydrogel has extended mucosal retention, strong antibacterial activity, and steady release of CBD. This underscores its significant potential as a targeted treatment for inflammatory oral diseases such as gingivitis and periodontitis.