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Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions

Jungmi Park1, Neel Mahida1, Gabrielle Ho1

  • 1Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USA.

Antibiotics (Basel, Switzerland)
|August 26, 2023
PubMed

Insights

Biodegradable nanoemulsions effectively deliver pseudopyronine analogs (PAs) to eradicate biofilms. This approach enhances solubility and penetration, offering a promising solution for multi-drug-resistant bacterial infections.

Area of Science:

  • Nanotechnology
  • Microbiology
  • Pharmaceutical Sciences

Background:

  • Multi-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), present a significant healthcare challenge.
  • Small molecule antimicrobials (SMAs), such as α-pyrones, show potential against MDR infections but often suffer from poor solubility due to their hydrophobic nature.
  • The efficacy of SMAs is further limited in complex biological environments like bacterial biofilms.

Purpose of the Study:

  • To develop and evaluate biodegradable polymer nanoemulsions (BNEs) for encapsulating pseudopyronine analogs (PAs).
  • To enhance the solubility and delivery of hydrophobic PAs into bacterial biofilms for improved antimicrobial efficacy.
  • To assess the antibiofilm activity of PA-loaded BNEs against Gram-positive pathogens.

Main Methods:

  • A series of pseudopyronine analogs (PAs) with varying alkyl chain lengths were synthesized and evaluated for antimicrobial activity.
  • The most potent PA was selected and encapsulated into biodegradable polymer nanoemulsions (BNEs) to create PA-BNEs.
  • The efficacy of PA-BNEs against Gram-positive bacterial biofilms, including MRSA, was assessed, focusing on solubility and penetration into the biofilm matrix.

Main Results:

  • The BNE formulation successfully solubilized the hydrophobic PAs, enabling effective delivery deep into the biofilm extracellular polymeric substance (EPS) matrix.
  • The PA-BNEs demonstrated significant antimicrobial efficacy against biofilms of Gram-positive strains.
  • The pseudopyronine analog PA2 exhibited synergistic antibiofilm activity when encapsulated within the nanoemulsions.

Conclusions:

  • Biodegradable polymer nanoemulsions provide a viable platform for overcoming the solubility and delivery limitations of hydrophobic small molecule antimicrobials.
  • PA-BNEs offer a promising strategy for the efficient eradication of bacterial biofilms, particularly those caused by multi-drug-resistant pathogens.
  • This approach represents a novel therapeutic avenue for combating challenging biofilm infections in healthcare settings.
Keywords:
biofilm infectionsessential oilsnanoemulsionspseudopyronine analogs

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