Preclinical Validation of MIN-T: A Novel Controlled-Released Formulation for the Adjunctive Local Application of...

Background: Adjunctive treatment of periodontitis lacks solutions which allow for enough time for wound healing in the periodontal pockets by avoiding fast re-colonization. Such a solution might be an antibiotic-containing formulation with a controlled release over a period of weeks. Here, a recently described minocycline-containing approach is qualified for further clinical development by focusing on proof-of-concept, systemic burden, resistance development, and degradation studies. Methods: Animal studies were done in two different (mouse-chamber, rat Porphyromonas gingivalis challenging) models, including effects on inflammation markers, bone loss, and bone structure. Also, serum concentrations of minocycline after local application were determined by HPLC-MS/MS. The resistance status of bacterial clinical isolates against minocycline was investigated and the degradation of the formulation was characterized by laser scanning and scanning electron microscopy. Results: Animal studies clearly demonstrated the applicability of the new formulation in the investigated models. Inflammation markers decreased in a dose-dependent manner and reduced bone loss compared to non-treated group was observed. Therefore, the systemic burden of the antibiotic was neglectable. Minocycline is still effective against oral pathogens; resistance development was not seen. The biodegradable thread was first swollen and subsequently degraded over a period of weeks. Conclusions: The results support the continued clinical development of this new formulation. A phase I clinical trial is planned to further evaluate its safety and efficacy.