Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus

Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is challenging modern antimicrobial therapy due to its high antimicrobial resistance. Nutraceuticals have gained a lot of interest and their incorporation into nanoparticles further improves their efficacy. This study aimed to evaluate the...

Full description

Saved in:
Bibliographic Details
Main Authors: Gaidaa M. Dogheim, Michael G. Shehat, Dina M. Mahdy, Hebatallah S. Barakat, Alaa Abouelfetouh, Alyaa A. Ramadan
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-95343-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849713540664918016
author Gaidaa M. Dogheim
Michael G. Shehat
Dina M. Mahdy
Hebatallah S. Barakat
Alaa Abouelfetouh
Alyaa A. Ramadan
author_facet Gaidaa M. Dogheim
Michael G. Shehat
Dina M. Mahdy
Hebatallah S. Barakat
Alaa Abouelfetouh
Alyaa A. Ramadan
author_sort Gaidaa M. Dogheim
collection DOAJ
description Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is challenging modern antimicrobial therapy due to its high antimicrobial resistance. Nutraceuticals have gained a lot of interest and their incorporation into nanoparticles further improves their efficacy. This study aimed to evaluate the antibacterial activity of linalool-based lipid nanocapsules loaded with resveratrol (LIN-LNC-RES) as a synergistic strategy against MRSA. LIN-LNC-RES were prepared by the phase inversion temperature method and characterized for their colloidal properties, in vitro release, and stability. The antibacterial and antibiofilm activity against S. aureus and different MRSA clinical isolates were investigated. Furthermore, scanning electron microscopy (SEM) imaging for visualization of biofilm formation and bacterial membrane integrity as well as mechanistic investigation using quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed. LIN-LNCs-RES demonstrated favorable properties with a size of 35.19 ± 0.72 nm, PDI of 0.09 ± 0.02 and a zeta potential of -2.53 ± 0.07 mV with RES 98% EE. They showed a controlled release of RES over 24 h and were stable at 4 °C for 3 months. Compared to free drug, LIN-LNC-RES showed a 4-fold decrease in MIC values and 10-fold decrease in half maximal biofilm inhibitory concentration value. Biofilm eradication assay showed superiority of LIN-LNC-RES over RES against all isolates with disrupted bacterial membranes as revealed by SEM. Mechanistically, qRT-PCR showed that LIN-LNC-RES significantly reduced RNAIII gene expression as well as the expression of SaeRS two component system, potentially affecting quorum sensing and virulence factors expression. RES-loaded LIN-based nanosystem offers a great potential for combating MRSA infections, neutralizing its virulence activity hence, overcoming antimicrobial resistance.
format Article
id doaj-art-8fc12083908f43398ef073ac90dc8335
institution DOAJ
issn 2045-2322
language English
publishDate 2025-04-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-8fc12083908f43398ef073ac90dc83352025-08-20T03:13:55ZengNature PortfolioScientific Reports2045-23222025-04-0115112110.1038/s41598-025-95343-wAntibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureusGaidaa M. Dogheim0Michael G. Shehat1Dina M. Mahdy2Hebatallah S. Barakat3Alaa Abouelfetouh4Alyaa A. Ramadan5Pharmaceutics department, Faculty of Pharmacy, Alexandria UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Alexandria UniversityPharmaceutics Department, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport (AASTMT)Pharmaceutics department, Faculty of Pharmacy, Alexandria UniversityDepartment of Microbiology and Immunology, Faculty of Pharmacy, Alexandria UniversityPharmaceutics department, Faculty of Pharmacy, Alexandria UniversityAbstract Methicillin-resistant Staphylococcus aureus (MRSA) is challenging modern antimicrobial therapy due to its high antimicrobial resistance. Nutraceuticals have gained a lot of interest and their incorporation into nanoparticles further improves their efficacy. This study aimed to evaluate the antibacterial activity of linalool-based lipid nanocapsules loaded with resveratrol (LIN-LNC-RES) as a synergistic strategy against MRSA. LIN-LNC-RES were prepared by the phase inversion temperature method and characterized for their colloidal properties, in vitro release, and stability. The antibacterial and antibiofilm activity against S. aureus and different MRSA clinical isolates were investigated. Furthermore, scanning electron microscopy (SEM) imaging for visualization of biofilm formation and bacterial membrane integrity as well as mechanistic investigation using quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed. LIN-LNCs-RES demonstrated favorable properties with a size of 35.19 ± 0.72 nm, PDI of 0.09 ± 0.02 and a zeta potential of -2.53 ± 0.07 mV with RES 98% EE. They showed a controlled release of RES over 24 h and were stable at 4 °C for 3 months. Compared to free drug, LIN-LNC-RES showed a 4-fold decrease in MIC values and 10-fold decrease in half maximal biofilm inhibitory concentration value. Biofilm eradication assay showed superiority of LIN-LNC-RES over RES against all isolates with disrupted bacterial membranes as revealed by SEM. Mechanistically, qRT-PCR showed that LIN-LNC-RES significantly reduced RNAIII gene expression as well as the expression of SaeRS two component system, potentially affecting quorum sensing and virulence factors expression. RES-loaded LIN-based nanosystem offers a great potential for combating MRSA infections, neutralizing its virulence activity hence, overcoming antimicrobial resistance.https://doi.org/10.1038/s41598-025-95343-wLipid nanocapsulesNutraceuticalsResveratrolMRSAAntimicrobial resistance
spellingShingle Gaidaa M. Dogheim
Michael G. Shehat
Dina M. Mahdy
Hebatallah S. Barakat
Alaa Abouelfetouh
Alyaa A. Ramadan
Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus
Scientific Reports
Lipid nanocapsules
Nutraceuticals
Resveratrol
MRSA
Antimicrobial resistance
title Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus
title_full Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus
title_fullStr Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus
title_full_unstemmed Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus
title_short Antibacterial and anti-virulence activity of eco-friendly resveratrol-loaded lipid nanocapsules against methicillin-resistant staphylococcus aureus
title_sort antibacterial and anti virulence activity of eco friendly resveratrol loaded lipid nanocapsules against methicillin resistant staphylococcus aureus
topic Lipid nanocapsules
Nutraceuticals
Resveratrol
MRSA
Antimicrobial resistance
url https://doi.org/10.1038/s41598-025-95343-w
work_keys_str_mv AT gaidaamdogheim antibacterialandantivirulenceactivityofecofriendlyresveratrolloadedlipidnanocapsulesagainstmethicillinresistantstaphylococcusaureus
AT michaelgshehat antibacterialandantivirulenceactivityofecofriendlyresveratrolloadedlipidnanocapsulesagainstmethicillinresistantstaphylococcusaureus
AT dinammahdy antibacterialandantivirulenceactivityofecofriendlyresveratrolloadedlipidnanocapsulesagainstmethicillinresistantstaphylococcusaureus
AT hebatallahsbarakat antibacterialandantivirulenceactivityofecofriendlyresveratrolloadedlipidnanocapsulesagainstmethicillinresistantstaphylococcusaureus
AT alaaabouelfetouh antibacterialandantivirulenceactivityofecofriendlyresveratrolloadedlipidnanocapsulesagainstmethicillinresistantstaphylococcusaureus
AT alyaaaramadan antibacterialandantivirulenceactivityofecofriendlyresveratrolloadedlipidnanocapsulesagainstmethicillinresistantstaphylococcusaureus