Hyaluronic acid-based minocycline-loaded dissolving microneedle: Innovation in local minocycline delivery for periodontitis

Periodontitis is a prevalent inflammatory disease that affects tooth-supporting tissues and is induced by complex polymicrobial dental plaques. Prior treatments, including topical antibiotic ointments, have faced difficulties in tissue permeability issues. Although dissolving microneedle (DMN) has been proposed as a painless and highly efficient transdermal drug delivery system to resolve this challenge, minocycline, widely used for the treatment of periodontitis, is light-sensitive, making it challenging to maintain its stability using conventional fabrication methods. Our hyaluronic acid-based minocycline-loaded dissolving microneedle (HAM-DMN) was designed utilizing an innovative light-blocking strategy, preserving 94.4 % of minocycline's stability, as confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. HAM-DMNs demonstrated antimicrobial efficacy in in vitro zone of inhibition tests with Streptococcus mutans strains and provided enhanced local delivery of minocycline to porcine oral gingival mucosa at concentrations 6.1 times higher than those of commercial ointments. In vivo studies in periodontitis-induced rat models showed that HAM-DMNs reduced levels of junctional epithelium more effectively than control and blank DMN groups, indicating enhanced treatment efficacy. HAM-DMN is a novel local delivery system developed to overcome the limitations of systemic delivery and conventional topical treatment. We suggest that HAM-DMNs can replace injections for the treatment of intraoral mucosal and systemic diseases.