Enhanced efficacy against bacterial biofilms via host:guest cyclodextrin‐doxycycline inclusion complexes

Abstract

Periodontal disease is characterized by a microbial infection and it is one of the major causes of teeth loss. The growth of pathogenic bacteria in oral cavity, such as Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), provides a favorable enviromment for the biofilm formation, which result in periodontal diseases. The development of new technologies to potentiate existing drugs, avoiding bacterial biofilms resistance and improving chemical stability is highly desirable. Here, we report the use of host–guest chemistry to enhance the activity of antibacterial doxycycline (DOX) in A. actinomycetemcomitans bacterial strain suspension and biofilm in vitro through complexation with hydroxypropyl-β-cyclodextrin (HPβCD) using different molar ratios of DOX/HPβCD. 2D 1H NMR confirmed the host–guest complexation of DOX and HPβCD. We assessed the colloidal characteristics of the complex DOX/HPβCD via Dynamic Light Scattering (DLS) and Zeta Potential (PZ). The mixing ratio 1:2 DOX/HPβCD significantly decreased the minimum inhibitory concentration (MIC) and improved efficacy against A. actinomycetemcomitans suspensions and biofilms, respectively, when compared to free DOX and other DOX/HPβCD complexes. Further, the interaction of different molar ratio proportions of DOX/HPβCD complex with bacterial membrane was demonstrated via Isothermal Titration Calorimetry (ITC). Thus, we suggested the enhanced efficacy of the DOX/HPβCD complexes, at molar ratio 1:2, is due the higher cyclodextrin ratio, which potentiate the interaction between drug and bacterial membrane through nonionic interactions, such as hydrogen bonding or other van der Waals interactions. Collectively, the development of these complexes enables increased efficacy against bacterial biofilms, which hold promise for the treatment of aggressive and non-responsive forms of periodontitis.

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Data availability

All data and material available upon request.

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Acknowledgements

We are grateful for CNPq, CAPES, FAPEMIG, INCT/Nanobiofar that support this investigation. The authors also thank Professor Gustavo Menezes, Immunobiophotonics Lab, Universidade Federal de Minas Gerais (UFMG) for technical support and constructive advice.

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CNPq, CAPES, FAPEMIG, INCT/Nanobiofar that support this investigation.

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PPGG, ACM, MEC and RDS conceived the ideas, designed the experiments, interpreted the data and wrote the manuscript. PPGG, ACM, KIRT, AMLD, and RAF conducted the experiments and analyzed the data. All authors discussed the results and commented on the manuscript.

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Correspondence to Rubén Dario Sinisterra.

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Guimarães, P.P.G., de Menezes, A.C., Teixeira, K.I.R. et al. Enhanced efficacy against bacterial biofilms via host:guest cyclodextrin‐doxycycline inclusion complexes. J Incl Phenom Macrocycl Chem (2021). https://doi.org/10.1007/s10847-020-01041-7

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Keywords

  • Doxycycline
  • Hydroxypropyl-β-cyclodextrin
  • Inclusion complexes
  • Drug delivery
  • Biofilm
  • Aggregatibacter actinomycetemcomitans