Scientific article
OA Policy
English

Dhvar5-chitosan nanogels and their potential to improve antibiotics activity

Published inInternational journal of biological macromolecules, vol. 277, no. Pt 1, 134059
Publication date2024-10
First online date2024-07-10
Abstract

Infection is one of the main causes of orthopedic implants failure, with antibiotic-resistant bacteria playing a crucial role in this outcome. In this work, antimicrobial nanogels were developed to be applied in situ as implant coating to prevent orthopedic-device-related infections. To that regard, a broad-spectrum antimicrobial peptide, Dhvar5, was grafted onto chitosan via thiol-norbornene "photoclick" chemistry. Dhvar5-chitosan nanogels (Dhvar5-NG) were then produced using a microfluidic system. Dhvar5-NG (1010 nanogels (NG)/mL) with a Dhvar5 concentration of 6 μg/mL reduced the burden of the most critical bacteria in orthopedic infections - methicillin-resistant Staphylococcus aureus (MRSA) - after 24 h in medium supplemented with human plasma proteins. Transmission electron microscopy showed that Dhvar5-NG killed bacteria by membrane disruption and cytoplasm release. No signs of cytotoxicity against a pre-osteoblast cell line were verified upon incubation with Dhvar5-NG. To further explore therapeutic alternatives, the potential synergistic effect of Dhvar5-NG with antibiotics was evaluated against MRSA. Dhvar5-NG at a sub-minimal inhibitory concentration (109 NG/mL) demonstrated synergistic effect with oxacillin (4-fold reduction: from 2 to 0.5 μg/mL) and piperacillin (2-fold reduction: from 2 to 1 μg/mL). This work supports the use of Dhvar5-NG as adjuvant of antibiotics to the prevention of orthopedic devices-related infections.

Keywords
  • Antimicrobial peptides
  • Chitosan nanoparticles
  • Oxacillin
  • Piperacillin
  • Synergistic effect
  • Thiol−ene click chemistry
  • Chitosan / chemistry
  • Chitosan / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / chemistry
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Microbial Sensitivity Tests
  • Humans
  • Nanogels / chemistry
  • Antimicrobial Peptides / chemistry
  • Antimicrobial Peptides / pharmacology
  • Cell Line
  • Mice
  • Animals
Affiliation entities Not a UNIGE publication
Citation (ISO format)
COSTA, B et al. Dhvar5-chitosan nanogels and their potential to improve antibiotics activity. In: International journal of biological macromolecules, 2024, vol. 277, n° Pt 1, p. 134059. doi: 10.1016/j.ijbiomac.2024.134059
Main files (1)
Article (Published version)
Identifiers
Journal ISSN0141-8130
5views
7downloads

Technical informations

Creation08/10/2025 10:34:11
First validation17/11/2025 10:38:49
Update time17/11/2025 10:38:49
Status update17/11/2025 10:38:49
Last indexation17/11/2025 10:38:49
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack