Sulfobutylether-β-Cyclodextrin inclusion complex improves the activity of rutin against resistant strains

Alternative strategies to conventional antibiotics are needed to fight resistant pathogens. Flavonoids, bioactive metabolites from plants, could be promising agents to treat, alone or in combination with antibiotics, infections caused by resistant and biofilm producing bacteria. However, their clinical employment is underexploited due to their low water solubility. Rutin (RTN) is a flavonoid with anti-inflammatory, anticancer, antioxidant and antibacterial activity. Cyclodextrins (CDs), cyclic oligosaccharides, able to interact with hydrophobic molecules to form inclusion complexes, could be used to overcome the low water solubility of rutin, in order to increase its bioavailability and to improve stability. The aim of this study was designed a liquid formulation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating bacterial infections. A deep physical–chemical characterization of the RTN/SBE-β-CD inclusion complex showed the formation of a stable complex with higher water solubility. The antibacterial activity of the RTN/SBE-β-CD inclusion complex, compared to both free RTN and SBE-β-CD, was assayed against S. aureus and P. aeruginosa strains. The maximum RTN concentration tested was 1250 μg/mL as soluble RTN/SBE-β-CD inclusion complex, 150 μg/mL for free RTN (maximum solubility). Complexed RTN showed bactericidal activity against S. aureus ATCC 6538, S. aureus ATCC 43300 (MRSA) and P. aeruginosa ATCC 9027, bacteriostatic activity against P. aeruginosa DSM 102273, resistant strain. Moreover, the inclusion complex significantly decreased biofilm biomass and cell viability at 0.5 MIC against S. aureus ATCC 6538 and S. aureus MRSA. Free RTN showed bacteriostatic activity against S. aureus ATCC 6538 and P. aeruginosa ATCC 9027 and no activity against the resistant strains. The results suggest that SBE-β-CD could be a suitable carrier for RTN, permitting the realization of liquid formulation with antibacterial properties and representing a good starting point for successive studies such as combinatorial activity of RTN with conventional antibiotics.