Journal
CARBOHYDRATE POLYMERS
Volume 234, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.115928
Keywords
Drug-resistant bacterial; Nitric oxide; Methicillin; Antibacterial; PAMAM; Chitosan
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Funding
- National Natural Science Foundation of China [51573071]
- Science and Technology Program of Guangzhou, China [201904010145]
- Chinese Fundamental Research Funds for the Central Universities, GDHVPS (2017)
- Science and technology innovation platform project of Foshan City, China [2017AG100092]
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We developed a co-delivery system of nitric oxide (NO) and antibiotic for the antibiotic-resistant bacterial infection therapy. The NO could disperse the bacterial biofilms and convert the bacteria into an antibiotic-susceptible planktonic form. Using the chitosan-graft-poly(amidoamine) dendrimer (CS-PAMAM) as the co-delivery system, methicillin (MET) and NO were conjugated successively to form CS-PAMAM-MET/NONOate. The positive CS-PAMAM could efficiently capture the negatively charged bacteria and PAMAM provide abundant reaction points for high payloads of NO and MET. The CS-PAMAM-MET/NONOate displayed effective and combined antibacterial activity to the E. coli and S. aureus. Particularly, for the MET-resistant S. aureus (MRSA), the CS-PAMAM-MET/NONOate displayed the synergistic antibacterial activity. In vivo wound healing assays also confirmed that CS-PAMAM-MET/NONOate could heal the infection formed by MRSA and then accelerate the wound healing effectively. Moreover, CS-PAMAM-MET/NONOate showed no toxicity towards 3T3 cells in vitro and rats in vivo, providing a readily but high-efficient strategy to drug-resistant bacterial infection therapy.
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