The Incorporation of CBD into Biodegradable DL-Lactide/Glycolide Copolymers Creates a Persistent Antibacterial Environment: An In Vitro Study on Streptococcus mutans and Staphylococcus aureus

<b>Background</b>: Cannabidiol (CBD) is a natural compound from the <i>Cannabis sativa</i> L. plant, which has anti-inflammatory, anti-nociceptive, neuroprotective, and antibacterial activities. <b>Objective</b>: The aim of this study was to develop a sustained-release device of CBD that can provide an antibacterial effect against the Gram-positive bacteria <i>Streptococcus mutans</i> and <i>Staphylococcus aureus</i> for extended periods of time. <b>Methods</b>: CBD was incorporated into the biodegradable PURASORB 5010 or PURASORB 7510 DL-lactide/glycolide polymers using either dimethylsulfoxide (DMSO) or acetone as the solvent, and the dried polymer scaffolds were exposed daily to a fresh culture of bacteria. The bacterial growth was determined daily by optical density, and the metabolic activity of biofilms was determined using the MTT assay. Biofilm formation on the polymer scaffolds was visualized by HR-SEM. Its anti-inflammatory effect was determined by measuring the IL-6 release from LPS-stimulated RAW 264.7 macrophages by ELISA. Cell cytotoxicity on normal Vero epithelial cells was determined by the MTT assay. The daily release of CBD was determined by gas chromatography-mass spectrometry (GC-MS). <b>Results</b>: PURASORB 5010/CBD scaffolds had antibacterial activity against <i>S. mutans</i> UA159, <i>S. aureus</i> ATCC25923, and a clinical isolate of a multidrug-resistant <i>S. aureus</i> (MDRSA CI-M) strain for the tested period of up to 17 days. PURASORB 7510/CBD scaffolds also had antibacterial activity, but overall, it was less effective than PURASORB 5010/CBD over time. The addition of PEG400 to the copolymers significantly increased the antibacterial activity of PURASORB 7510/CBD but not of PURASORB 5010/CBD. The daily release of CBD from the polymer scaffolds was sufficient to reduce the LPS-induced IL-6 secretion from RAW 264.7 macrophages, and importantly, it was not cytotoxic to either RAW 264.7 macrophages or Vero epithelial cells. The daily release of CBD was found to be between 1.12 and 9.43 µg/mL, which is far below the cytotoxic dose of 25 µg/mL. <b>Conclusions</b>: The incorporation of CBD into the biodegradable PURASORB 5010 can be used to prepare sustained-release devices for medical purposes where combined antibacterial and anti-inflammatory activities are desirable.