4.8 Article

Triclosan-based supramolecular hydrogels as nanoantibiotics for enhanced antibacterial activity

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 324, Issue -, Pages 354-365

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2020.05.034

Keywords

Self-assembling peptide; Supramolecular hydrogel; Triclosan; Nanoantibiotic; Antibacterial

Funding

  1. National Natural Science Foundation of China [21708048, 81722026, 51703247, 31771085]
  2. CAMS Innovation Fund for Medical Sciences [2016-I2M-3-022, 2017I2M-2-004]
  3. Science Foundation for Distinguished Young Scholars of Tianjin [18JCJQJC47300, 19JCJQJC62200]
  4. Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2018PT35031, 2019-RC-HL-014]
  5. Drug Innovation Major Project [2018ZX09711-001-005]
  6. National University of Singapore [R279-000-482-133]

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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.

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