4.2 Article

Mannosylated Gold Nanoclusters Incorporated with a Repurposed Antihistamine Drug Promethazine for Antibacterial and Antibiofilm Applications

Journal

ACS APPLIED BIO MATERIALS
Volume 5, Issue 12, Pages 5911-5923

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsabm.2c00867

Keywords

repurposing; antihistamine; nanoclusters; mannosylation; antibacterial; antibiofilm

Funding

  1. School of Health Science Technology
  2. Department of Biotechnology, Government of India for Translation Programme in the DBT Programme Support Facility, Indian Institute of Technology, Guwahati, India [BT/PR44695/NER/95/1880/2021, BT/PR41449/NER/95/1687/837 2020]
  3. Centre for Nanotechnology (ICMR Centre for Excellence) at IIT Guwahati [5/3/8/20/2019-ITR, 5(1)/2021-NANO]
  4. Science and Engineering Research Board [JCB/2019/000039]

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Drug repurposing is a feasible strategy for addressing antibiotic resistance. This study explored the antimicrobial properties of the commonly used antihistamine drug, promethazine, in both Gram-positive and Gram-negative bacteria. By combining promethazine with nanoscale materials, such as mannose-conjugated bovine serum albumin-stabilized gold nanoclusters, the efficiency of the drug can be enhanced. The study found that the drug-loaded gold nanoclusters effectively targeted bacteria through the inhibition of their adhesive appendage called pili, resulting in bacterial inhibition and potential biofilm eradication.
Drug repurposing presents a workable strategy in tackling antibiotic resistance. Many known drugs have been repurposed for their applications against different targets. Antihistamines that are usually used to treat allergy symptoms can be combined with nanoscale materials to enhance their efficiency. Herein, we explored the antimicrobial properties of a common antihistamine drug, promethazine, in Gram-positive and Gram-negative bacteria. Being positively charged, promethazine was easily incorporated into the mannose-conjugated bovine serum albumin-stabilized promethazine hydrochloride gold nanoclusters. Capping with n-mannose helped in targeting the bacteria by inhibiting their adhesive appendage called pili. Following their uptake, drugs released inside the bacteria caused reactive oxygen species production and membrane permeability alteration, ultimately resulting in bacterial inhibition. Additionally, they were also explored for biofilm eradication. As observed through staining assays, the number of dead cells increased with increasing concentration of drug-loaded gold nanoclusters in the biofilm mass. Therefore, the as-synthesized mannosylated gold nanoclusters incorporated with promethazine were analyzed for potential antibacterial and antibiofilm applications.

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