Clinical Oral Investigations

, Volume 22, Issue 3, pp 1243–1252 | Cite as

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

  • Jadesada Palasuk
  • L. Jack Windsor
  • Jeffrey A. Platt
  • Yuri Lvov
  • Saulo Geraldeli
  • Marco C. BottinoEmail author
Original Article



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.


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.


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.


Dental adhesive Matrix metalloproteinase Halloysite® Doxycycline Nanotubes 



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.


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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Jadesada Palasuk
    • 1
    • 2
  • L. Jack Windsor
    • 2
  • Jeffrey A. Platt
    • 2
  • Yuri Lvov
    • 3
  • Saulo Geraldeli
    • 4
  • Marco C. Bottino
    • 5
    Email author
  1. 1.Department of Restorative Dentistry, Faculty of DentistryNaresuan UniversityPhitsanulokThailand
  2. 2.Department of Biomedical and Applied SciencesIndiana University School of DentistryIndianapolisUSA
  3. 3.Institute for MicromanufacturingLouisiana Tech UniversityRustonUSA
  4. 4.Department of Restorative Dental Sciences, Operative Division, College of DentistryUniversity of FloridaGainesvilleUSA
  5. 5.Department of Cariology, Restorative Sciences, and EndodonticsUniversity of Michigan School of DentistryAnn ArborUSA

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