Methicillin-resistant Staphylococcus aureus (MRSA) infections account for a sanitary emergency in the clinic. Sepsis induced by MRSA leads to a marked aggressiveness of the infection, associated with a "cytokine-storm" that can is responsible for higher mortality due to multi-organ failure.
The discovery of new antibiotics, with immunomodulatory functions associated to an efficient antibacterial profile, is ideal to develop new therapies for MRSA-induced sepsis. Cannabis sativa-derived cannabinoids showed an intriguing antibacterial activity and, particularly, a significant killing activity against gram positive bacteria, including MRSA. Among different phytocannabinoids, cannabidiol (CBD) exerts a wide range of antioxidant, antinflammatory and immunoregulatory functions, including NO downregulation and iNOS protein expression inhibition in different experimental conditions and, in particular, during LPS-induced intestinal inflammation. Such activity is coupled to a safe profile in humans, whereas CBD lacks any psychotropic activity. In the attempt to increase CBD antibacterial activiy and pharmacokinetic potential, we will develop a series of CBD-related synthetic analogues (CBDrsa), by chemical elongation of pentyl chain of the CBD naïve molecule, and we will maximize drug permeabilization through the targeted bacteria and hosting tissues, through the encapsulation of both CBD and CBDrsa in niosomes or nanogels. We will explore the antimicrobial efficacy of CBD and CBDrsa, as nude molecules or vehicle-carried by niosomal and nanogel formulations, on reference strains of S. aureus/S. epidermidis spp and clinical MRSA isolates.
Since CBD is already available in the clinic as antiepileptic drug in Dravet syndrome, depending upon the successful results obtained by this research project, we will perform in vivo studies to propose the repositioning of this molecule or its derivatives as new class of antibiotic.
