Dual antimicrobial-loaded biodegradable nanoemulsions for synergistic treatment of wound biofilms

Ahmed Nabawy; Jessa Marie Makabenta; Suzannah Schmidt-Malan; Jungmi Park; Cheng-Hsuan Li; Rui Huang; Stefano Fedeli; Aritra Nath Chattopadhyay; Robin Patel; Vincent M Rotello

doi:10.1016/j.jconrel.2022.05.013

Dual antimicrobial-loaded biodegradable nanoemulsions for synergistic treatment of wound biofilms

J Control Release. 2022 Jul:347:379-388. doi: 10.1016/j.jconrel.2022.05.013. Epub 2022 May 18.

Authors

Affiliations

¹ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: anabawy@umass.edu.
² Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: jmakabenta@umass.edu.
³ Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America. Electronic address: SchmidtMalan.Suzannah@mayo.edu.
⁴ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: jungmipark@umass.edu.
⁵ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: chenghsuanli@umass.edu.
⁶ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: ruihuang@umass.edu.
⁷ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: sfedeli@umass.edu.
⁸ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: aritranathch@umass.edu.
⁹ Division of Clinical Microbiology, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, United States of America. Electronic address: patel.robin@mayo.edu.
¹⁰ Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, United States. Electronic address: rotello@chem.umass.edu.

Abstract

Wound biofilm infections caused by multidrug-resistant (MDR) bacteria constitute a major threat to public health; acquired resistance combined with resistance associated with the biofilm phenotype makes combatting these infections challenging. Biodegradable polymeric nanoemulsions that encapsulate two hydrophobic antimicrobial agents (eugenol and triclosan) (TE-BNEs) as a strategy to combat chronic wound infections are reported here. The cationic nanoemulsions efficiently penetrate and accumulate in biofilms, synergistically eradicating MDR bacterial biofilms, including persister cells. Notably, the nanoemulsion platform displays excellent biocompatibility and delays emergence of resistance to triclosan. The TE-BNEs are active in an in vivo murine model of mature MDR wound biofilm infections, with 99% bacterial elimination. The efficacy of this system coupled with prevention of emergence of bacterial resistance highlight the potential of this combination platform to treat MDR wound biofilm infections.

Keywords: Antimicrobials; In vivo; Multidrug-resistant bacteria; Nanoemulsions; Wound biofilms.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Anti-Infective Agents*
Biofilms
Drug Resistance, Multiple, Bacterial
Mice
Microbial Sensitivity Tests
Triclosan* / chemistry
Triclosan* / pharmacology

Substances

Anti-Bacterial Agents
Anti-Infective Agents
Triclosan

Grants and funding

R01 AI134770/AI/NIAID NIH HHS/United States