Sustained Release of Minocycline From Minocycline-Calcium-Dextran Sulfate Complex Microparticles for Periodontitis Treatment

J Pharm Sci. 2018 Dec;107(12):3134-3142. doi: 10.1016/j.xphs.2018.08.023. Epub 2018 Sep 7.

Abstract

It is important to address the periodontitis-associated bacteria in the residual subgingival plaque after scaling and root planing to successfully treat periodontitis. In this study, we explored the possibility of exploiting the ion pairing/complexation of minocycline, Ca2+, and sulfate/sulfonate-bearing biopolymers to develop an intrapocket delivery system of minocycline as an adjunct to scaling and root planing. Minocycline-calcium-dextran sulfate complex microparticles were synthesized from minocycline, CaCl2, and dextran sulfate. They were characterized using Fourier-transform infrared spectroscopy, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. An in vitro release study was conducted to evaluate the release kinetics of minocycline from these microparticles. Agar disk diffusion assays and biofilm-grown bacteria assays were used to assess antibacterial capability. High loading efficiency (96.98% ± 0.12%) and high loading content (44.69% ± 0.03%) for minocycline were observed for these complex microparticles. Mino-Ca-DS microparticles achieved sustained release of minocycline for at least 9 days at pH 7.4 and 18 days at pH 6.4 in phosphate-buffered saline, respectively. They also demonstrated potent antimicrobial effects against Streptococcus mutans and Aggregatibacter actinomycetemcomitans in agar disk diffusion and biofilm assays. These results suggested that the ion pairing/complexation of minocycline, Ca2+, and sulfonate/sulfate-bearing biopolymers can be exploited to develop complex microparticles as local delivery systems for periodontitis treatment.

Keywords: complexation; controlled release; drug delivery system; microbiome; microparticles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggregatibacter actinomycetemcomitans / drug effects
  • Aggregatibacter actinomycetemcomitans / physiology
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Biofilms / drug effects
  • Calcium / chemistry*
  • Cell Line
  • Delayed-Action Preparations / chemistry*
  • Dextran Sulfate / chemistry*
  • Drug Liberation
  • Humans
  • Minocycline / administration & dosage*
  • Minocycline / chemistry
  • Minocycline / pharmacology
  • Pasteurellaceae Infections / drug therapy
  • Periodontitis / drug therapy
  • Streptococcus mutans / drug effects
  • Streptococcus mutans / physiology

Substances

  • Anti-Bacterial Agents
  • Delayed-Action Preparations
  • Dextran Sulfate
  • Minocycline
  • Calcium