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

Multi-drug-resistant (MDR) bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), pose a significant challenge in healthcare settings. Small molecule antimicrobials (SMAs) such as α-pyrones have shown promise as alternative treatments for MDR infections. However,...

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Main Authors: Jungmi Park, Neel Mahida, Gabrielle Ho, Elizabeth Pena, Jessa Marie V. Makabenta, Stanley Aneke, Mingdi Jiang, Leah M. Bouthillette, Stephanie E. Holz, Muhammad Aamir Hassan, Amanda L. Wolfe, Vincent M. Rotello
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/12/8/1240
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author Jungmi Park
Neel Mahida
Gabrielle Ho
Elizabeth Pena
Jessa Marie V. Makabenta
Stanley Aneke
Mingdi Jiang
Leah M. Bouthillette
Stephanie E. Holz
Muhammad Aamir Hassan
Amanda L. Wolfe
Vincent M. Rotello
author_facet Jungmi Park
Neel Mahida
Gabrielle Ho
Elizabeth Pena
Jessa Marie V. Makabenta
Stanley Aneke
Mingdi Jiang
Leah M. Bouthillette
Stephanie E. Holz
Muhammad Aamir Hassan
Amanda L. Wolfe
Vincent M. Rotello
author_sort Jungmi Park
collection DOAJ
description Multi-drug-resistant (MDR) bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), pose a significant challenge in healthcare settings. Small molecule antimicrobials (SMAs) such as α-pyrones have shown promise as alternative treatments for MDR infections. However, the hydrophobic nature of many SMAs limits their solubility and efficacy in complex biological environments. In this study, we encapsulated pseudopyronine analogs (PAs) in biodegradable polymer nanoemulsions (BNEs) for efficient eradication of biofilms. We evaluated a series of PAs with varied alkyl chain lengths and examined their antimicrobial activity against Gram-positive pathogens (<i>S. aureus</i>, MRSA, and <i>B. subtilis</i>). The selected PA with the most potent antibiofilm activity was incorporated into BNEs for enhanced solubility and penetration into the EPS matrix (PA-BNEs). The antimicrobial efficacy of PA-BNEs was assessed against biofilms of Gram-positive strains. The BNEs facilitated the solubilization and effective delivery of the PA deep into the biofilm matrix, addressing the limitations of hydrophobic SMAs. Our findings demonstrated that the PA2 exhibited synergistic antibiofilm activity when it was loaded into nanoemulsions. This study presents a promising platform for addressing MDR infections by combining pseudopyronine analogs with antimicrobial biodegradable nanoemulsions, overcoming challenges associated with treating biofilm infections.
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spelling doaj.art-8f44b28528ae4c819935c5f3f0cb30372023-11-18T23:58:51ZengMDPI AGAntibiotics2079-63822023-07-01128124010.3390/antibiotics12081240Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine AnalogsJungmi Park0Neel Mahida1Gabrielle Ho2Elizabeth Pena3Jessa Marie V. Makabenta4Stanley Aneke5Mingdi Jiang6Leah M. Bouthillette7Stephanie E. Holz8Muhammad Aamir Hassan9Amanda L. Wolfe10Vincent M. Rotello11Department of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry and Biochemistry, University of North Carolina Asheville, Asheville, NC 28804, USADepartment of Chemistry and Biochemistry, University of North Carolina Asheville, Asheville, NC 28804, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USADepartment of Chemistry and Biochemistry, University of North Carolina Asheville, Asheville, NC 28804, USADepartment of Chemistry, University of Massachusetts Amherst, Amherst, MA 01003, USAMulti-drug-resistant (MDR) bacteria, including methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), pose a significant challenge in healthcare settings. Small molecule antimicrobials (SMAs) such as α-pyrones have shown promise as alternative treatments for MDR infections. However, the hydrophobic nature of many SMAs limits their solubility and efficacy in complex biological environments. In this study, we encapsulated pseudopyronine analogs (PAs) in biodegradable polymer nanoemulsions (BNEs) for efficient eradication of biofilms. We evaluated a series of PAs with varied alkyl chain lengths and examined their antimicrobial activity against Gram-positive pathogens (<i>S. aureus</i>, MRSA, and <i>B. subtilis</i>). The selected PA with the most potent antibiofilm activity was incorporated into BNEs for enhanced solubility and penetration into the EPS matrix (PA-BNEs). The antimicrobial efficacy of PA-BNEs was assessed against biofilms of Gram-positive strains. The BNEs facilitated the solubilization and effective delivery of the PA deep into the biofilm matrix, addressing the limitations of hydrophobic SMAs. Our findings demonstrated that the PA2 exhibited synergistic antibiofilm activity when it was loaded into nanoemulsions. This study presents a promising platform for addressing MDR infections by combining pseudopyronine analogs with antimicrobial biodegradable nanoemulsions, overcoming challenges associated with treating biofilm infections.https://www.mdpi.com/2079-6382/12/8/1240biofilm infectionsnanoemulsionspseudopyronine analogsessential oils
spellingShingle Jungmi Park
Neel Mahida
Gabrielle Ho
Elizabeth Pena
Jessa Marie V. Makabenta
Stanley Aneke
Mingdi Jiang
Leah M. Bouthillette
Stephanie E. Holz
Muhammad Aamir Hassan
Amanda L. Wolfe
Vincent M. Rotello
Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
Antibiotics
biofilm infections
nanoemulsions
pseudopyronine analogs
essential oils
title Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
title_full Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
title_fullStr Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
title_full_unstemmed Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
title_short Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
title_sort integration of antimicrobials and delivery systems synergistic antibiofilm activity with biodegradable nanoemulsions incorporating pseudopyronine analogs
topic biofilm infections
nanoemulsions
pseudopyronine analogs
essential oils
url https://www.mdpi.com/2079-6382/12/8/1240
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