Author(s):
Machado, Fátima Alexandra Meira ; Gama, F. M. ; Martins, J. A. R.
Date: 2024
Persistent ID: https://hdl.handle.net/1822/93703
Origin: RepositóriUM - Universidade do Minho
Project/scholarship:
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIO%2F04469%2F2019/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FQUI%2F00686%2F2019/PT;
info:eu-repo/grantAgreement/FCT/POR_NORTE/SFRH%2FBD%2F132000%2F2017/PT;
Subject(s): Bone infections; Dextrinvitamin D3; Hydrophobic interactions
Description
In this work, an expedite synthesis was developed for a self-assembled micelle carrier for the antimicrobial peptide LL18. Covalent one-pot functionalization of dextrin with succinylated vitamin D3 and succinic anhydride produced an amphiphilic material that undergoes self-assembly into micelles in aqueous medium. Succinylated dextrinvitamin D3 micelles were efficiently loaded with LL18 by electrostatic and hydrophobic interactions. Remarkably, the LL18-loaded micelle formulation dramatically improves the antibacterial activity of free LL18 against S. aureus, completely abrogates its severe hemolytic activity, redirects the internalization of LL18 from the perinuclear region of osteoblasts to the lysosomes and reduces cellular toxicity towards osteoblasts and macrophages. Overall, this work demonstrates that self-assembled micelle formulations based on dextrin, vitamin D3 and antimicrobial peptides, are promising platforms to develop multifunctional antibiotic-independent antimicrobial agents, not prone to the development of bacterial resistance, to treat bone infections.
The authors acknowledge the funding from FEDER and NORTE 2020 through the project no. 003262 titled ‘‘iBONE therapies: advanced solutions for bone regeneration’’. This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469 and UID/QUI/00686/2019 units and COMPETE 2020 (POCI-01-0145-FEDER-006684) and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte 2020 – Programa Operacional Regional do Norte. Alexandra Machado gratefully acknowledges FCT for the granted scholarship (SFRH/BD/132000/2017).
info:eu-repo/semantics/publishedVersion
