# Development of Freeze-Dried Hyaluronic Acid Sheets for Healing Oral Mucositis: Influence of Hyaluronic Acid Molecular Weight and Nicotinamide Mononucleotide Loading on Healing Efficacy

## TL;DR

Researchers developed freeze-dried hyaluronic acid sheets to treat oral mucositis, finding that sheets with 800 kDa HA and nicotinamide mononucleotide are most effective.

## Contribution

The study introduces an optimized hyaluronic acid sheet formulation with specific molecular weight and NMN loading for enhanced healing of oral mucositis.

## Key findings

- 800 kDa hyaluronic acid sheets showed the greatest healing efficacy in an animal model.
- Hyaluronic acid sheets with nicotinamide mononucleotide demonstrated sustained release and good buccal retention.
- Hyaluronic acid with or without NMN was non-toxic in in vitro cytotoxicity assays.

## Abstract

Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This study aimed to optimize the HA sheet formulation by evaluating the effects of HA molecular weight and nicotinamide mononucleotide (NMN) loading on therapeutic efficacy. HA sheets were prepared using HA with four different molecular weights (50, 350, 800, and 2000 kDa), and their therapeutic effects were evaluated in an animal oral ulcer model using 6-week-old male Syrian hamsters. Among the formulations tested, the 800 kDa HA sheet exhibited the greatest healing efficacy, and it showed an excellent balance between buccal retention and the sustained release of NMN for the treatment of oral mucositis. In vitro cytotoxicity assays confirmed that HA, with or without NMN, was non-toxic and suitable for local applications. These findings indicate that HA sheets, particularly those composed of 800 kDa HA, may represent a promising and biocompatible mucoadhesive material for the delivery of NMN and the local treatment of oral mucositis associated with head and neck cancer.