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

## TL;DR

A new drug delivery method using the maxillofacial route was tested in humans and showed effective low-dose systemic delivery of metronidazole without side effects.

## Contribution

A novel maxillofacial drug delivery platform was tested in a first-in-human trial for low-dose systemic delivery of metronidazole.

## Key findings

- Maxillofacial delivery provided significant systemic exposure with an 80-fold lower dose than oral administration.
- Systemic drug exposure was comparable between maxillofacial and oral delivery when using raw AUC values.
- No local or systemic adverse events were observed in either group.

## Abstract

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.