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Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion

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Abstract

Objectives

This article evaluated the drug loading, release kinetics, and matrix metalloproteinase (MMP) inhibition of doxycycline (DOX) released from DOX-loaded nanotube-modified adhesives. DOX was chosen as the model drug, since it is the only MMP inhibitor approved by the U.S. Food and Drug Administration.

Materials and methods

Drug loading into the nanotubes was accomplished using DOX solution at distinct concentrations. Increased concentrations of DOX significantly improved the amount of loaded DOX. The modified adhesives were fabricated by incorporating DOX-loaded nanotubes into the adhesive resin of a commercial product. The degree of conversion (DC), Knoop microhardness, DOX release kinetics, antimicrobial, cytocompatibility, and anti-MMP activity of the modified adhesives were investigated.

Results

Incorporation of DOX-loaded nanotubes did not compromise DC, Knoop microhardness, or cell compatibility. Higher concentrations of DOX led to an increase in DOX release in a concentration-dependent manner from the modified adhesives. DOX released from the modified adhesives did not inhibit the growth of caries-related bacteria, but more importantly, it did inhibit MMP-1 activity.

Conclusions

The loading of DOX into the nanotube-modified adhesives did not compromise the physicochemical properties of the adhesives and the released levels of DOX were able to inhibit MMP activity without cytotoxicity.

Clinical significance

Doxycycline released from the nanotube-modified adhesives inhibited MMP activity in a concentration-dependent fashion. Therefore, the proposed nanotube-modified adhesive may hold clinical potential as a strategy to preserve resin/dentin bond stability.

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Acknowledgements

We thank Dr. Bruce Cooper (Bindley Bioscience Center, Purdue University) for the assistance in HPLC and mass spectrometry analyses, Dr. Richard L. Gregory (IUSD) for the access to his microbiology facilities, and Caroline Miller (Indiana University, School of Medicine) for the TEM study. This manuscript is based on a dissertation submitted to the graduate faculty, Indiana University Purdue University (IUPUI), in partial fulfillment of the requirements for the Doctor of Philosophy Degree in Dental Sciences.

Funding

This study was supported in part by a grant from the Delta Dental Foundation (MCB).

Author information

Authors and Affiliations

  1. Department of Restorative Dentistry, Faculty of Dentistry, Naresuan University, Phitsanulok, 65000, Thailand

    Jadesada Palasuk

  2. Department of Biomedical and Applied Sciences, Indiana University School of Dentistry, Indianapolis, IN, 46202, USA

    Jadesada Palasuk, L. Jack Windsor & Jeffrey A. Platt

  3. Institute for Micromanufacturing, Louisiana Tech University, Ruston, LA, 71272, USA

    Yuri Lvov

  4. Department of Restorative Dental Sciences, Operative Division, College of Dentistry, University of Florida, Gainesville, FL, 32610, USA

    Saulo Geraldeli

  5. Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, 1011 N. University Avenue, Ann Arbor, MI, 48109, USA

    Marco C. Bottino

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  1. Jadesada Palasuk
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  2. L. Jack Windsor
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Correspondence to Marco C. Bottino.

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Palasuk, J., Windsor, L.J., Platt, J.A. et al. Doxycycline-loaded nanotube-modified adhesives inhibit MMP in a dose-dependent fashion. Clin Oral Invest 22, 1243–1252 (2018). https://doi.org/10.1007/s00784-017-2215-y

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  • DOI: https://doi.org/10.1007/s00784-017-2215-y

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