Antimicrobial Activity Enhancers: Towards Smart Delivery of Antimicrobial Agents

Skwarczynski, Mariusz; Bashiri, Sahra; Yuan, Ye; Ziora, Zyta M.; Nabil, Osama; Masuda, Keita; Khongkow, Mattaka; Rimsueb, Natchanon; Cabral, Horacio; Ruktanonchai, Uracha; Blaskovich, Mark A. T.; Toth, Istvan

doi:10.3390/antibiotics11030412

Cited by 43 publications

(18 citation statements)

References 219 publications

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“…However, to ensure the efficient delivery of all components to the target site, "smart" drug delivery systems may be employed, where the antimicrobial agents could be encapsulated and released at the infection site in response to a stimuli/trigger. 56 This could be an attractive avenue to increase the feasibility of this trisystem strategy for clinical applications. It is envisaged that the tri-system will most likely be more suitable for topical (local) or intravenous than oral administration routes in humans because of the potential degradation of antimicrobial agents in the gastrointestinal tract.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…While there may be concerns regarding the feasibility of having all 3 components at the infection site in vivo, recent studies on binary combination systems involving antimicrobial polymers have shown the successful translation of in vitro antimicrobial efficacies to in vivo animal models (via intraperitoneal and tail vein injections in mouse). , This offers hope that the tri-systems demonstrated here may achieve similar potency in vivo as the in vitro results. However, to ensure the efficient delivery of all components to the target site, “smart” drug delivery systems may be employed, where the antimicrobial agents could be encapsulated and released at the infection site in response to a stimuli/trigger . This could be an attractive avenue to increase the feasibility of this tri-system strategy for clinical applications.…”

Section: Resultsmentioning

confidence: 99%

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Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics

et al. 2022

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The escalating issue of multidrug-resistant (MDR) bacteria indicates the urgent need for new and effective strategies to combat this global health challenge. Here, we describe a new combinatorial approach that can be put forward for experimental therapy application against MDR bacteria. Specifically, we have developed a tri-system that includes the coadministration of two different membrane-disrupting-type antimicrobial agentsa synthetic antimicrobial polymer P and an antimicrobial peptide (AMP) colistin methanesulfonate (Col)in conjunction with an antibiotic [doxycycline (Dox), rifampicin (Rif), or azithromycin (Azi)]. Traditionally, the administration of membrane-disrupting antimicrobial agents causes toxicity, but, in comparison, we demonstrated synergy and biocompatibility using this combinatorial approach. Checkerboard assays showed the occurrence of synergistic interactions in Col-Dox-P, Col-Rif-P, and Col-Azi-P tri-systems against wild-type and MDR Pseudomonas aeruginosa, with the Col-Dox-P system being the most effective. The ability to synergize thus enables the use of a lower dosage in combinations compared to the standalone agents. The tri-systems not only demonstrated bacteriostatic activity but were also bactericidal. For example, the Col-Dox-P system (at 8, 4, and 8 μg mL–1, respectively) and the Col-Rif-P system (at 4, 8, and 16 μg mL–1, respectively) were able to kill >99.999% of planktonic P. aeruginosa cells within 3 h of treatment. More importantly, an improvement of the therapeutic/selectivity index was achieved via combination therapy. Taking the Col-Dox-P system as an example, its biocompatibility with murine embryonic fibroblast cells was found to be comparable to that of polymer P alone despite the synergistic enhancement in antimicrobial activity of the combination. This resulted in a significant increase in selectivity by 16-fold for the Col-Dox-P combination system compared to P alone. Furthermore, the broad applicability of this tri-system strategy was demonstrated via the successful application of the AMP melittin in place of Col or P. Overall, this study sheds new insights on the application of membrane-disrupting antimicrobial agents in combination therapy and their potential for safer clinical use. Additionally, the information gathered in this study could inform the development of future combination therapy systems involving the simultaneous employment of multiple AMPs with antibiotics.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics

et al. 2022

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“…In this regard, curcuminoids, particularly CUR, have been complexed with various metals to achieve the desired synergistic effects. These formulations include curcumin–tannic acid-metal complexes (CUR-TA-Fe II and CUR-TA-Fe III) [ 101 ], curcumin–zinc oxide nanoparticles [ 102 ], and gallium–curcumin nanoparticles [ 103 ]. CUR has been reported to possess varying degrees of activity against the following viruses: high-risk human papillomaviruses, coxsackievirus, hepatitis C, herpes simplex virus type 1, influenza viruses (PR8, H1N1, and H6N1), and transmissible gastroenteritis virus [ 100 ].…”

Section: Notable Bioactivitiesmentioning

confidence: 99%

Bioactive Compounds from the Zingiberaceae Family with Known Antioxidant Activities for Possible Therapeutic Uses

et al. 2022

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The Zingiberaceae family is a rich source of diverse bioactive phytochemicals. It comprises about 52 genera and 1300 species of aromatic flowering perennial herbs with characteristic creeping horizontal or tuberous rhizomes. Notable members of this family include ginger (Zingiber officinale Roscoe), turmeric (Curcuma longa L.), Javanese ginger (Curcuma zanthorrhiza Roxb.), and Thai ginger (Alpinia galanga L.). This review focuses on two main classes of bioactive compounds: the gingerols (and their derivatives) and the curcuminoids. These compounds are known for their antioxidant activity against several maladies. We highlight the centrality of their antioxidant activities with notable biological activities, including anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, antimicrobial, and anticancer effects. We also outline various strategies that have been applied to enhance these activities and make suggestions for research areas that require attention.

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“…In this review, we report and discuss the latest strategies presented in the literature to circumvent Gram-negative bacterial resistance. This review will not deal with immunoconjugates or aptamer strategies, since numerous reviews have been devoted to this strategy [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives

Tabcheh

Vergalli

Davin-Régli

et al. 2023

IJMS

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Antibiotic resistance continues to evolve and spread beyond all boundaries, resulting in an increase in morbidity and mortality for non-curable infectious diseases. Due to the failure of conventional antimicrobial therapy and the lack of introduction of a novel class of antibiotics, novel strategies have recently emerged to combat these multidrug-resistant infectious microorganisms. In this review, we highlight the development of effective antibiotic combinations and of antibiotics with non-antibiotic activity-enhancing compounds to address the widespread emergence of antibiotic-resistant strains.

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Antimicrobial Activity Enhancers: Towards Smart Delivery of Antimicrobial Agents

Cited by 43 publications

References 219 publications

Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics

Two plus One: Combination Therapy Tri-systems Involving Two Membrane-Disrupting Antimicrobial Macromolecules and Antibiotics

Bioactive Compounds from the Zingiberaceae Family with Known Antioxidant Activities for Possible Therapeutic Uses

Rejuvenating the Activity of Usual Antibiotics on Resistant Gram-Negative Bacteria: Recent Issues and Perspectives

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