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. 2023 Nov 20;6(11):4805-4813.
doi: 10.1021/acsabm.3c00576. Epub 2023 Oct 20.

Synergistic Combination of Antimicrobial Peptides and Cationic Polyitaconates in Multifunctional PLA Fibers

Alberto Chiloeches  1   2 , Jakub Zágora  3 , Daniela Plachá  3 , Marcelo D T Torres  4   5   6 , Cesar de la Fuente-Nunez  4   5   6 , Fátima López-Fabal  7   8 , Yolanda Gil-Romero  7 , Raquel Fernández-García  7 , Marta Fernández-García  1 , Coro Echeverría  1 , Alexandra Muñoz-Bonilla  1
Affiliations

Synergistic Combination of Antimicrobial Peptides and Cationic Polyitaconates in Multifunctional PLA Fibers

Alberto Chiloeches et al. ACS Appl Bio Mater. .

Abstract

Combining different antimicrobial agents has emerged as a promising strategy to enhance efficacy and address resistance evolution. In this study, we investigated the synergistic antimicrobial effect of a cationic biobased polymer and the antimicrobial peptide (AMP) temporin L, with the goal of developing multifunctional electrospun fibers for potential biomedical applications, particularly in wound dressing. A clickable polymer with pendent alkyne groups was synthesized by using a biobased itaconic acid building block. Subsequently, the polymer was functionalized through click chemistry with thiazolium groups derived from vitamin B1 (PTTIQ), as well as a combination of thiazolium and AMP temporin L, resulting in a conjugate polymer-peptide (PTTIQ-AMP). The individual and combined effects of the cationic PTTIQ, Temporin L, and PTTIQ-AMP were evaluated against Gram-positive and Gram-negative bacteria as well as Candida species. The results demonstrated that most combinations exhibited an indifferent effect, whereas the covalently conjugated PTTIQ-AMP displayed an antagonistic effect, potentially attributed to the aggregation process. Both antimicrobial compounds, PTTIQ and temporin L, were incorporated into poly(lactic acid) electrospun fibers using the supercritical solvent impregnation method. This approach yielded fibers with improved antibacterial performance, as a result of the potent activity exerted by the AMP and the nonleaching nature of the cationic polymer, thereby enhancing long-term effectiveness.

Keywords: antimicrobial; antimicrobial peptide; cationic polymers; fibers; supercritical impregnation.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Synthesis of cationic biobased polyitaconate bearing thiazolium groups (PTTIQ) and of the conjugated structure, biobased polyitaconate bearing thiazolium and AMP (PTTIQ-AMP).
Figure 2
Figure 2
1H NMR spectra of (A) PTTIQ and (B) PTTIQ-AMP biobased polymer.
Figure 3
Figure 3
FTIR spectra of PTTIQ, temporin L peptide, and the PTTIQ-AMP conjugated polymer.
Figure 4
Figure 4
SEM images of prepared fiber mats before (PLA and PLA/PTTIQ) and after (PLA + AMP and PLA/PTTIQ + AMP) scCO2 impregnation with AMP.
Figure 5
Figure 5
FTIR spectra of nonimpregnated fibers (PLA and PLA/PTTIQ) and impregnated fibers with AMP (PLA + AMP and PLA/PTTIQ + AMP).
Figure 6
Figure 6
Photographs of disk diffusion assays on agar plates cultivated with Gram-negative E. coli of nonimpregnated fibers (PLA and PLA/PTTIQ) and impregnated fibers with AMP (PLA + AMP and PLA/PTTIQ + AMP).
See this image and copyright information in PMC

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