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Keywords = PABN

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11 pages, 1765 KB  
Article
Integration of Antimicrobials and Delivery Systems: Synergistic Antibiofilm Activity with Biodegradable Nanoemulsions Incorporating Pseudopyronine Analogs
by 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 and Vincent M. Rotello
Antibiotics 2023, 12(8), 1240; https://doi.org/10.3390/antibiotics12081240 - 28 Jul 2023
Cited by 5 | Viewed by 2625
Abstract
Multi-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (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 [...] Read more.
Multi-drug-resistant (MDR) bacteria, including methicillin-resistant Staphylococcus aureus (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 (S. aureus, MRSA, and B. subtilis). 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. Full article
(This article belongs to the Special Issue Design and Synthesis of Novel Antibiotics)
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18 pages, 4369 KB  
Article
The Impact of an Efflux Pump Inhibitor on the Activity of Free and Liposomal Antibiotics against Pseudomonas aeruginosa
by Douweh Leyla Gbian and Abdelwahab Omri
Pharmaceutics 2021, 13(4), 577; https://doi.org/10.3390/pharmaceutics13040577 - 18 Apr 2021
Cited by 19 | Viewed by 4042
Abstract
The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, [...] Read more.
The eradication of Pseudomonas aeruginosa in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against P. aeruginosa isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on P. aeruginosa biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 ± 33.74 nm for gentamicin and 3086.35 ± 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 ± 1.54% and 51.58 ± 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4–32 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients. Full article
(This article belongs to the Special Issue Polymers Enhancing Bioavailability in Drug Delivery)
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