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Delivery of cyclodextrin polymers to bacterial biofilms - An exploratory study using rhodamine labelled cyclodextrins and multiphoton microscopy

Journal article
Authors Hanna Thomsen
Gábor Benkovics
Éva Fenyvesi
Anne Farewell
Milo Malanga
Marica B Ericson
Published in International Journal of Pharmaceutics
Volume 531
Issue 2
Pages 650-657
ISSN 0378-5173
Publication year 2017
Published at Department of Chemistry and Molecular Biology
Centre for antibiotic resistance research, CARe
Pages 650-657
Language en
Keywords Charge functionalization, Cyclodextrin polymers, Multiphoton laser scanning microscopy, Rhodamine, Spectral analysis, Staphylococcus epidermidis biofilm
Subject categories Nano Technology, Microbiology, Biophysical chemistry


© 2017 The Authors. Cyclodextrin (CD) polymers are interesting nanoparticulate systems for pharmaceutical delivery; however, knowledge regarding their applications towards delivery into complex microbial biofilm structures is so far limited. The challenge is to demonstrate penetration and transport through the biofilm and its exopolysaccharide matrix. The ideal functionalization for penetration into mature biofilms is unexplored. In this paper, we present a novel set of rhodamine labelled βCD-polymers, with different charge moieties, i.e., neutral, anionic, and cationic, and explore their potential delivery into mature Staphylococcus epidermidis biofilms using multiphoton laser scanning microscopy (MPM). The S. epidermidis biofilms, being a medically relevant model organism, were stained with SYTO9. By using MPM, three-dimensional imaging and spectral investigation of the distribution of the βCD-polymers could be obtained. It was found that the cationic βCD-polymers showed significantly higher integration into the biofilms, compared to neutral and anionic functionalized βCDs. None of the carriers presented any inherent toxicity to the biofilms, meaning that the addition of rhodamine moiety does not affect the inertness of the delivery system. Taken together, this study demonstrates a novel approach by which delivery of fluorescently labelled CD nanoparticles to bacterial biofilms can be explored using MPM. Future studies should be undertaken investigating the potential in using cationic functionalization of CD based delivery systems for targeting anti-microbial effects in biofilms.

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