# Mucoadhesive Buccal Patches Containing Resveratrol and/or Erythromycin-Loaded Lipid Microparticles as a Potential Targeted Strategy for the Prevention and Management of MRONJ in Patients Undergoing Oral Surgery

## TL;DR

This study develops buccal patches with antibiotics and resveratrol to prevent MRONJ in patients undergoing oral surgery, avoiding systemic drug use.

## Contribution

A novel mucoadhesive buccal patch with antibiotic-loaded lipid microparticles for localized MRONJ prevention is proposed.

## Key findings

- Microparticles achieved high drug loading (≈90%) and were produced using a green method.
- Buccal patches showed strong mucoadhesion and delivered 25% erythromycin and 2% resveratrol to buccal tissue.
- The patches avoided systemic absorption while promoting local drug accumulation.

## Abstract

Background/Objectives: Oral surgical procedures in patients at risk of/diagnosed with MRONJ require systemic antibiotic therapy, which can fail to achieve an adequate local drug concentration. This research aims to design mucoadhesive buccal patches (containing erythromycin or the erythromycin–resveratrol combination) tailored to the therapeutic needs of patients at risk of MRONJ undergoing oral surgery. Methods: Erythromycin (ERY) and resveratrol (RSV) were embedded into lipid-based microparticles prepared via hot melt dispersion. The microparticles, recovered in the form of dry powders, were characterized in terms of yield, softening/melting temperature, active(s) content, physical state (amorphous vs. crystalline), and individual and bulk properties. Then, they were loaded into a hydrophilic gel, which was dried, obtaining microparticle-loaded buccal patches. The optimized patches were characterized in terms of uniformity, folding endurance, swelling, mucoadhesion, and oromucosal permeation/retention. Results: The microparticles were efficiently produced via a green approach, resulting in reproducible pharmaceutical powders with high loading efficacy (≈90%), spherical morphology, particle sizes in the range of approximately 106–425 μm, and a softening temperature close to body temperature. The buccal patches were also obtained via a green approach, and were found to be thin, flexible, homogeneous, highly swellable, extremely mucoadhesive, and able to promote ERY and RSV accumulation in the buccal tissue (≈25% and 2% of ERY and RSV, respectively, after 2 h) while avoiding active(s) absorption. Conclusions: The proposed buccal patches are viable candidates for further clinical trials aimed at evaluating both the effectiveness of locoregional antibiotic treatment and the usefulness of the co-administration of RSV and ERY.