Antibiofilm activity of lactose and κ-carrabiose chitosan derivates

• Chitosan derivatives with lactose and κ-carrabiose were synthesized and characterized. • Derivatives were evaluated for antimicrobial and antibiofilm activity against S. aureus. • Selected Cs derivatives inhibited early biofilm formation and reduced mature 24 h biofilms. • The chitoan-lactose derivative improved the antibiofilm efficacy of ciprofloxacin The use of natural polysaccharides, particularly chitosan and its derivatives, as agents to prevent biofilm formation and attenuate virulence properties of pathogenic bacteria has received increasing attention in recent years. In this study chitosan and some selected derivatives were tested for their antibacterial activity, with a N-alkylated lactose chitosan derivative and a N-alkylated κ-carrabiose chitosan derivative showing promising results as inhibitors of in vitro biofilm formation in the bacterial strain Staphylococcus aureus ATCC25923. In combination with the antibiotic ciprofloxacin, the selected lactose derivative showed a reduction in biofilm formation compared to the use of the antibiotic alone and was effective in alleviating the enhancement of biofilm formation that arrives as an unwanted effect of the antibiotic use. The novel κ-carrabiose-chitosan derivatives were synthesized using response surface methodology (RSM) and products with different degrees of substitution were obtained in a controlled manner. The reaction conditions were selected based on the prior optimization by RSM of the influential variables (reagent concentrations, volume, time and temperature) in the synthesis of lactose-chitosan derivatives. The reductive amination reaction using 2-picoline borane as a reducing agent was selected to achieve the synthesis of the chitosan derivatives, making the reaction and work-up greener and safer.