Sodium alginate/polycaprolactone co-axial wet-spun microfibers modified with N-carboxymethyl chitosan and the peptide AAPV for Staphylococcus aureus and human neutrophil elastase inhibition in potential chronic wound scenarios.

Autor: Miranda CS; Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azurém, 4800-058 Guimarães, Portugal. Electronic address: catarina.miranda@2c2t.uminho.pt., Silva AFG; Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. Electronic address: pg40181@alunos.uminho.pt., Seabra CL; Associate Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal. Electronic address: cseabra@ff.up.pt., Reis S; Associate Laboratory for Green Chemistry (LAQV), Network of Chemistry and Technology (REQUIMTE), Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal. Electronic address: shreis@ff.up.pt., Silva MMP; Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. Electronic address: nini@quimica.uminho.pt., Pereira-Lima SMMA; Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. Electronic address: silviap@quimica.uminho.pt., Costa SPG; Centre of Chemistry (CQ), University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal. Electronic address: spc@quimica.uminho.pt., Homem NC; Digital Transformation CoLab (DTx), Building 1, University of Minho, Campus of Azurém, 4800-058 Guimarães, Portugal. Electronic address: natalia.homem@dtx-colab.pt., Felgueiras HP; Centre for Textile Science and Technology (2C2T), University of Minho, Campus of Azurém, 4800-058 Guimarães, Portugal. Electronic address: helena.felgueiras@2c2t.uminho.pt.
Jazyk: angličtina
Zdroj: Biomaterials advances [Biomater Adv] 2023 Aug; Vol. 151, pp. 213488. Date of Electronic Publication: 2023 Jun 01.
DOI: 10.1016/j.bioadv.2023.213488
Abstrakt: In chronic wound (CW) scenarios, Staphylococcus aureus-induced infections are very prevalent. This leads to abnormal inflammatory processes, in which proteolytic enzymes, such as human neutrophil elastase (HNE), become highly expressed. Alanine-Alanine-Proline-Valine (AAPV) is an antimicrobial tetrapeptide capable of suppressing the HNE activity, restoring its expression to standard rates. Here, we proposed the incorporation of the peptide AAPV within an innovative co-axial drug delivery system, in which the peptide liberation was controlled by N-carboxymethyl chitosan (NCMC) solubilization, a pH-sensitive antimicrobial polymer effective against Staphylococcus aureus. The microfibers' core was composed of polycaprolactone (PCL), a mechanically resilient polymer, and AAPV, while the shell was made of the highly hydrated and absorbent sodium alginate (SA) and NCMC, responsive to neutral-basic pH (characteristic of CW). NCMC was loaded at twice its minimum bactericidal concentration (6.144 mg/mL) against S. aureus, while AAPV was loaded at its maximum inhibitory concentration against HNE (50 μg/mL), and the production of fibers with a core-shell structure, in which all components could be detected (directly or indirectly), was confirmed. Core-shell fibers were characterized as flexible and mechanically resilient, and structurally stable after 28-days of immersion in physiological-like environments. Time-kill kinetics evaluations revealed the effective action of NCMC against S. aureus, while elastase inhibitory activity examinations proved the ability of AAPV to reduce HNE levels. Cell biology testing confirmed the safety of the engineered fiber system for human tissue contact, with fibroblast-like cells and human keratinocytes maintaining their morphology while in contact with the produced fibers. Data confirmed the engineered drug delivery platform as potentially effective for applications in CW care.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE