Researchers from the University of Sydney have developed inhalable powders combining cannabidiol (CBD) and vancomycin that demonstrated strong, sustained bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) in laboratory tests.
Published in the International Journal of Pharmaceutics, the study found that pairing the two drugs eliminated three clinical MRSA strains more effectively than either treatment alone. In 24-hour time-kill assays, the combinations—particularly at a 1:1 mass ratio—produced rapid bacterial reductions within hours and maintained activity throughout the test period, avoiding regrowth seen with single-drug treatments.
To create a lung-targeted therapy, researchers co-spray dried CBD and vancomycin with trehalose dihydrate and leucine, producing hollow, wrinkled particles optimized for inhalation. All formulations achieved fine particle fractions under 5 microns of at least 30%, with the vancomycin-rich blend reaching about 53%. The aerodynamic properties suggest that a significant proportion of each inhaled dose could reach deep lung tissue.
CBD is known for its antimicrobial, anti-inflammatory, and immunomodulatory properties, but it can degrade under physiological conditions, notes the study’s researchers. Combining it with vancomycin, a first-line MRSA treatment, offered both fast and sustained bacterial killing while potentially allowing lower antibiotic doses, reducing risks of systemic side effects.
Importantly, the antimicrobial potency was preserved after spray drying. The authors say the results support further stability testing and in vivo studies, with the goal of developing an inhalable MRSA therapy that delivers high drug concentrations directly to the infection site while minimizing systemic exposure.
The study’s full abstract can be found below:
Methicillin-resistant Staphylococcus aureus (MRSA) can cause life-threatening respiratory infections. Conventional oral and parenteral antibiotic treatments are often inefficient in targeting the lower respiratory tract and could cause systemic adverse effects. In this study, the 24-hour time-kill assay revealed that the co-delivery of cannabidiol (CBD) and vancomycin synergistically eradicated three clinical strains of MRSA. The combinations had rapid and sustained bactericidal activity over 24 h at the ½ x minimum inhibitory concentration (MIC). Four synergistic mass ratios of CBD and vancomycin (1:1, 2:1, 1:3, and 1:6, respectively) were co-spray dried with trehalose dihydrate and leucine to form inhalable powders. The powders were evaluated for their physicochemical and antimicrobial properties, including particle size distribution and morphology, solid-state characteristics, water sorption behaviour, aerosol performance, and 24-hour time-kill assay. Scanning electron microscopy images showed that the particles of all formulations were hollow and wrinkled. X-ray diffraction analysis confirmed that all formulations were amorphous. Moreover, moisture-induced recrystallisation occurred between 70 % and 80 % relative humidity as determined by dynamic vapour sorption. The spray-dried combinations were inhalable, achieving a fine particle fraction < 5 µm of at least 30 % upon dispersion. The formulation with the highest vancomycin content had the highest fine particle fraction, reaching approximately 53 % for both drugs. The fine particle dose < 5 µm achieved drug concentrations above the MICs when dissolved in the lung fluid after inhalation. The antimicrobial activity of the combinations was preserved after spray drying. In conclusion, CBD and vancomycin formulations were stable, inhalable, and effective in vitro against MRSA clinical strains.
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