According to a new study published in ACS Omega, cannabidiol (CBD)-loaded hydrogel strongly inhibited Staphylococcus aureus, a bacterium responsible for many skin and soft-tissue infections, while remaining noncytotoxic to human skin cells. The researchers also developed a cannabinol (CBN) version that provided sustained cannabinoid release, although it did not show the same antibacterial effect.
The study, conducted by researchers from Universidad Alfonso X el Sabio and UCAM-Universidad Católica de Murcia in Spain, along with scientists from institutions in Italy and Ecuador. The researchers developed agar-xanthan gum hydrogels containing CBD or CBN encapsulated with hydroxypropyl-β-cyclodextrin (HP-β-CD), a compound used to improve the water solubility and delivery of hydrophobic molecules such as cannabinoids.
The team created four formulations: an unloaded hydrogel, a hydrogel containing HP-β-CD alone, a CBD-containing hydrogel and a CBN-containing hydrogel. Each cannabinoid-loaded disc contained approximately 90 micrograms of CBD or 60 micrograms of CBN. The materials were designed to act as localized delivery platforms that could gradually release cannabinoids into surrounding tissue while maintaining a hydrated, biocompatible environment.
Release testing found that both cannabinoids were successfully delivered from the hydrogels over a 72-hour period. CBD was released more rapidly, with the hydrogel releasing close to 100% of its approximately 90-microgram CBD load in phosphate-buffered saline within 12 to 24 hours. In water, release was slightly slower and eventually reached about 90% to 95%.
CBN showed a more gradual profile. About 85% to 90% of the approximately 60 micrograms of CBN was released in phosphate-buffered saline within 48 to 72 hours, compared with roughly 80% to 85% in water. Researchers said the release patterns were primarily driven by diffusion through the swollen hydrogel network.
The most notable antibacterial findings involved the CBD formulation. Researchers tested the hydrogels against S. aureus and Escherichia coli (E. coli) using both disk-diffusion experiments and liquid bacterial cultures. Only the CBD-containing hydrogel produced a clear zone of inhibition against S. aureus. None of the formulations produced a marked inhibition zone against E. coli.
After 24 hours in liquid cultures, the S. aureus sample containing the CBD hydrogel appeared completely clear, suggesting nearly complete suppression of bacterial growth. Optical-density measurements also fell close to baseline levels. In comparison, the control, cannabinoid-free and CBN-loaded formulations continued to show substantial bacterial growth. No significant inhibition of E. coli was observed with any of the hydrogels.
Researchers also tested the materials with human skin fibroblasts for seven days. There were no statistically significant differences in cell viability between the hydrogel formulations, and the cells continued to proliferate over the course of the experiment. Cell-adhesion measurements also found no significant differences between the hydrogels and control cells grown without the materials.
Microscopic analysis further showed that by day seven, fibroblasts had formed nearly confluent layers across the hydrogel surfaces, with no evidence of abnormal cell morphology or necrotic areas.
The findings remain preclinical, with the antibacterial and biocompatibility experiments conducted entirely in laboratory conditions. Researchers concluded that agar-xanthan hydrogels containing cyclodextrin-cannabinoid complexes could offer a promising platform for localized, controlled cannabinoid delivery, particularly for soft-tissue applications where sustained drug release and antibacterial activity may both be useful.
