Triclosan-based Supramolecular Hydrogels as Nanoantibiotics for Enhanced Antibacterial Activity

Abstract With the emergence of drug-resistant bacteria, conventional antibiotics are becoming increasingly ineffective for the treatment of bacterial infections. Nanomaterial-modified antibiotics, denoted as “nanoantibiotics”, can usually circumvent most of the shortcomings of conventional antibiotics, thus improving antibacterial activities. Here, we developed triclosan-based supramolecular hydrogel nanoantibiotics by conjugating small molecule antibiotic triclosan (TCS) to self-assembling peptides. The resultant nanoantibiotics presented many beneficial characteristics: (i) a stable three-dimensional nanofiber structure; (ii) increased TCS solubility by 850-fold; (iii) acid-responsive TCS release; (iv) favorable biocompatibility. In consequence, the nanoantibiotics showed potent in vitro broad-spectrum antibacterial activities against both Gram-positive and Gram-negative bacteria based on the cooperative effect of antibiotic TCS and the nanostructure-induced bacterial membrane disruption. Furthermore, the TCS-based supramolecular hydrogel nanoantibiotics exhibited enhanced antibacterial activities with low side effects, according to the in vivo antibacterial evaluation at the macro and micro level. Therefore, the simple and effective hydrogel nanoantibiotics developed here hold great potential for the treatment of intractable bacterial infections.