In silico design and mechanistic study of niosome-encapsulated curcumin against multidrug-resistant Staphylococcus aureus biofilms

Mohammad Khaleghian; Hamidreza Sahrayi; Yousef Hafezi; Mahshad Mirshafeeyan; Zahra Salehi Moghaddam; Bahareh Farasati Far; Hassan Noorbazargan; Amir Mirzaie; Qun Ren

doi:10.3389/fmicb.2023.1277533

In silico design and mechanistic study of niosome-encapsulated curcumin against multidrug-resistant Staphylococcus aureus biofilms

Front Microbiol. 2023 Nov 30:14:1277533. doi: 10.3389/fmicb.2023.1277533. eCollection 2023.

Authors

Mohammad Khaleghian¹, Hamidreza Sahrayi², Yousef Hafezi³, Mahshad Mirshafeeyan², Zahra Salehi Moghaddam⁴, Bahareh Farasati Far⁵, Hassan Noorbazargan⁶, Amir Mirzaie⁷, Qun Ren⁸

Affiliations

¹ Department of Chemistry, Payame Noor University, Tehran, Iran.
² Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, Iran.
³ School of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran.
⁴ Department of Microbial Biotechnology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
⁵ Department of Chemistry, Iran University of Science and Technology, Tehran, Iran.
⁶ Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
⁷ Department of Biology, Parand Branch, Islamic Azad University, Shahr-e Jadid-e Parand, Iran.
⁸ Laboratory for Biointerfaces, Empa, Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, Switzerland.

Abstract

Curcumin, an important natural component of turmeric, has been known for a long time for its antimicrobial properties. This study aimed to investigate the anti-biofilm action of the niosome-encapsulated curcumin and explore the involved anti-biofilm mechanism. In silico investigations of ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) were first performed to predict the suitability of curcumin for pharmaceutical application. Curcumin showed low toxicity but at the same time, low solubility and low stability, which, in turn, might reduce its antimicrobial activity. To overcome these intrinsic limitations, curcumin was encapsulated using a biocompatible niosome system, and an encapsulation efficiency of 97% was achieved. The synthesized curcumin-containing niosomes had a spherical morphology with an average diameter of 178 nm. The niosomal curcumin was capable of reducing multi-drug resistant (MDR) Staphylococcus aureus biofilm 2-4-fold compared with the free curcumin. The encapsulated curcumin also demonstrated no significant cytotoxicity on the human foreskin fibroblasts. To understand the interaction between curcumin and S. aureus biofilm, several biofilm-related genes were analyzed for their expression. N-acetylglucosaminyl transferase (IcaD), a protein involved in the production of polysaccharide intercellular adhesion and known to play a function in biofilm development, was found to be downregulated by niosomal curcumin and showed high binding affinity (-8.3 kcal/mol) with curcumin based on molecular docking analysis. Our study suggests that the niosome-encapsulated curcumin is a promising approach for the treatment of MDR S. aureus biofilm and can be extended to biofilms caused by other pathogens.

Keywords: ADME prediction; Staphylococcus aureus; anti-biofilm; curcumin; in silico studies; molecular docking; niosome.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Open access funding by Swiss Federal Laboratories for Materials Science and Technology (Empa).