First-in-Human Randomized Controlled Pilot Trial of a Maxillofacial Drug Delivery Platform for Low-Dose Systemic Delivery.

Background This randomized controlled trial (RCT) evaluated a novel maxillofacial drug delivery platform for safe, rapid, and controlled systemic delivery of a low dose of metronidazole through a maxillofacial route that bypasses gastrointestinal absorption and first-pass hepatic metabolism. Methods In this parallel-group, pilot RCT (n = 20), patients undergoing maxillary first molar endodontic therapy received either 400 mg of oral metronidazole (control group; n = 10) or 5 mg of metronidazole administered using the maxillofacial platform (study group; n = 10). Sixty blood samples were collected at baseline, 15 minutes, and 30 minutes to assess early systemic exposure. Three turbid samples from one patient in the study group were excluded, resulting in nine patients in the study group, 10 in the control group, and 57 plasma samples for high-performance liquid chromatography (HPLC) analysis. Plasma metronidazole concentrations were quantified using HPLC, and the area under the plasma concentration-time curve (AUC) was calculated to assess systemic drug exposure. Due to non-normal data distribution, non-parametric statistical analyses were performed. Local and systemic adverse events (AEs) were monitored throughout the study. Results Primary analysis using dose-normalized AUC (DN AUC) demonstrated significant early systemic exposure following maxillofacial administration, despite an 80-fold lower dose compared to oral delivery. Sensitivity analysis using raw AUC values showed comparable systemic exposure between the two groups, supporting the robustness of the findings. No local or systemic AEs were observed in either group. Conclusion The maxillofacial drug delivery platform demonstrates potential for safe and rapid systemic drug delivery at low doses.