A star copolymer consisting of a β-cyclodextrin core and poly(amidoamine) dendron arms for co-delivering nitric oxide and triclosan for combined antibacterial effect

Abstract To co-deliver the antibacterial agents of nitric oxide (NO) and triclosan (TCA) for a combined antimicrobial effect, a star copolymer consisting of a β-cyclodextrin core and poly(amidoamine) dendron arms (β-CD-PAMAM) was synthesized, and TCA was encapsulated into the hydrophobic core of β-CD and NO was conjugated with the PAMAM arms. The obtained β-CD-PAMAM/TCA/NONOate was expected to combine the biofilm dispersal effect of NO with the antibacterial effect of both NO and TCA. We demonstrated that β-CD-PAMAM/TCA/NONOate could release TCA and NO simultaneously and showed an excellent antibacterial effect on both gram-negative bacteria ( Escherichia coli ) and gram-positive bacteria ( Staphylococcus aureus ). β-CD-PAMAM/TCA/NONOate showed antibacterial effect by inhibiting and dispersing the biofilm, which is the bacterial barrier to antibacterial agents, and this effect was found to be higher than that of TCA or NO used alone. Benefited from the combined antibacterial effect, the excellent effect of β-CD-PAMAM/TCA/NONOate on anti-infection and wound healing was successfully achieved in vivo . Moreover, β-CD-PAMAM/TCA/NONOate showed slight toxicity in vitro and in vivo , suggesting a promising application in the antimicrobial field. Statement of Significance A star copolymer (β-CD-PAMAM) consisting of a β-cyclodextrin (β-CD) core and poly(amidoamine) dendron (PAMAM) arms was synthesized, and then TCA (triclosan, an antibacterial) was encapsulated into the hydrophobic core of β-CD and NO was conjugated with the PAMAM arms. The obtained β-CD-PAMAM/TCA/NONOate was expected to combine the biofilm dispersal effect of NO with the antibacterial effect of both NO and TCA. It was found that β-CD-PAMAM/TCA/NONOate showed an excellent antibacterial effect on both gram-negative bacteria ( Escherichia coli ) and gram-positive bacteria ( Staphylococcus aureus ), and the biofilm could be inhibited and dispersed completely. Particularly, the co-delivery strategy showed an excellent antibacterial effect in vitro and in vivo , much better than that of TCA or NO used alone, suggesting a synergistic antimicrobial effect.