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Dendritic Nanogels Directed Dual-Encapsulation Topical Delivery System of Antimicrobial Peptides Targeting Skin Infections
KTH Royal Institute of Technology, SWEDEN; Jilin University, China.
RISE Research Institutes of Sweden, Materials and Production, Chemistry, Biomaterials and Textiles. University of Gothenburg, Sweden.ORCID iD: 0000-0002-4270-8475
KTH Royal Institute of Technology, SWEDEN.
KTH Royal Institute of Technology, SWEDEN.
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2023 (English)In: Macromolecular Bioscience, ISSN 1616-5187, E-ISSN 1616-5195Article in journal (Refereed) Epub ahead of print
Abstract [en]

Antimicrobial peptides (AMPs) are promising antibacterial agents in the fight against multidrug resistant pathogens. However, their application to skin infections is limited by the absence of a realizable topical delivery strategy. Herein, a hybrid hierarchical delivery system for topical delivery of AMPs is accomplished through the incorporation of AMPs into dendritic nanogels (DNGs) and their subsequent embedding into poloxamer gel. The high level of control over the crosslink density and the number of chosen functionalities makes DNGs ideal capsules with tunable loading capacity for DPK-060, a human kininogen-derived AMP. Once embedded into the poloxamer gel, DPK-060 encapsulated in DNGs displays a slower release rate compared to those entrapped directly in the gels. In vitro EpiDerm Skin Irritation Tests show good biocompatibility, while MIC and time-kill curves reveal the potency of the peptide toward Staphylococcus aureus. Anti-infection tests on ex vivo pig skin and in vivo mouse infection models demonstrate that formulations with 0.5% and 1% AMPs significantly inhibit the growth of S. aureus. Similar outcomes are observed for an in vivo mouse surgical site infection model. Importantly, when normalizing the bacteria inhibition to released/free DPK-060 at the wound site, all formulations display superior efficacy compared to DPK-060 in solution. © 2023 The Authors. 

Place, publisher, year, edition, pages
John Wiley and Sons Inc , 2023.
Keywords [en]
antimicrobial peptide delivery, dendritic nanogel, DPK-060, poloxamer gel, Antimicrobial agents, Bacteria, Biocompatibility, Mammals, Nanostructured materials, Peptides, Antimicrobial peptide, Dendritics, Nanogels, Peptide delivery, Poloxamer, Topical delivery
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:ri:diva-63994DOI: 10.1002/mabi.202200433Scopus ID: 2-s2.0-85146683018OAI: oai:DiVA.org:ri-63994DiVA, id: diva2:1737130
Note

Funding details: Knut och Alice Wallenbergs Stiftelse, 2012‐0196, 2017‐0300, 2019‐0002; Funding details: Vetenskapsrådet, VR, 2010–453; Funding details: Seventh Framework Programme, FP7, 60418; Funding details: Barncancerfonden, TJ2017‐0009; Funding text 1: The authors acknowledge the Knut och Alice Wallenberg Foundation (KAW) (Grant numbers: 2012‐0196, 2017‐0300, and 2019‐0002), the Seventh Framework Programme (Grant number: 60418), the Barncancerfonden (Grant number: TJ2017‐0009), and the Swedish Research Council (VR) (Grant number 2010–453) for financial support.

Available from: 2023-02-15 Created: 2023-02-15 Last updated: 2023-05-22Bibliographically approved

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Håkansson, Joakim

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