Doxycycline hydrochloride-metronidazole solid lipid microparticles gels for treatment of periodontitis: development, in-vitro and in-vivo clinical evaluation

Expert Opin Drug Deliv. 2017 Nov;14(11):1241-1251. doi: 10.1080/17425247.2017.1329297. Epub 2017 May 29.

Abstract

Objective: To formulate solid lipid microparticles (SLMs) encapsulating doxycycline hydrochloride (DH) and metronidazole (MT) for the treatment of periodontal diseases.

Methods: SLMs were prepared applying hot homogenization method, using different types of lipids and stabilized with various types and concentrations of surfactants. The optimized formula was subjected to freeze-drying followed by incorporation into poloxamer gel. Microbiological and clinical evaluation of the selected SLMs on patients suffering from periodontal diseases was performed.

Results: SLMs could entrap high percentage of both drugs (81.14% and 68.75 % for doxycycline hydrochloride and metronidazole respectively). Transmission electron microscopy images of SLMs showed nearly spherical particles. Freeze-dried SLMs showed satisfactory stability for three months. Combined drugs were molecularly dispersed in SLMs. Incorporation of the freeze-dried SLMs powder in poloxamer gel could control the drugs release for 72 h. In-vivo study revealed effective and safe use of SLMs gel for periodontitis treatment. Significant improvement in both microbiological and clinical parameters was observed as compared to scaling and root planing alone.

Conclusion: The formulated SLMs gel offers an applicable dosage form that can be injected directly into the periodontal pocket as adjunctive to scaling and root planing.

Keywords: Clinical study; doxycycline hydrochloride; freeze-drying; metronidazole; periodontitis; solid lipid microparticles.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / therapeutic use
  • Dental Scaling
  • Double-Blind Method
  • Doxycycline / administration & dosage*
  • Doxycycline / chemistry
  • Doxycycline / therapeutic use
  • Drug Combinations
  • Female
  • Gels / administration & dosage*
  • Gels / chemistry
  • Gels / therapeutic use
  • Humans
  • Lipids / chemistry
  • Male
  • Metronidazole / administration & dosage*
  • Metronidazole / chemistry
  • Metronidazole / therapeutic use
  • Middle Aged
  • Periodontitis / drug therapy*
  • Periodontitis / therapy
  • Surface-Active Agents / chemistry
  • Young Adult

Substances

  • Anti-Bacterial Agents
  • Drug Combinations
  • Gels
  • Lipids
  • Surface-Active Agents
  • Metronidazole
  • Doxycycline