# Adhesive hydrogel delivering ALA prevents the malignant transformation of oral leukoplakia

## TL;DR

A new adhesive hydrogel improves photodynamic therapy for oral leukoplakia by delivering a drug more effectively and reducing cancer risk.

## Contribution

A mucoadhesive hydrogel for sustained ALA delivery in oral PDT, enhancing drug retention and therapeutic outcomes.

## Key findings

- The ALA-Gel hydrogel showed excellent wet adhesion and sustained ALA release in the oral environment.
- In vitro and in vivo tests demonstrated potent cytotoxicity in leukoplakia cells with high biocompatibility.
- Clinical trials showed superior therapeutic outcomes compared to conventional treatments.

## Abstract

Photodynamic therapy (PDT) has shown promising efficacy for oral leukoplakia (OLK); however, its effectiveness is often compromised by the dynamic and wet oral environment, which impedes drug retention and complicates the maintenance of therapeutic concentrations. To overcome these limitations, we developed a mucoadhesive hydrogel composed of acrylic acid (AA), chitosan (CHI), and polydopamine for the controlled delivery of 5-aminolevulinic acid (ALA). The resulting ALA-loaded hydrogel (ALA-Gel) was synthesized via chemical cross-linking and demonstrated excellent wet adhesion capable of withstanding salivary flow, alongside sustained ALA release profiles. In vitro, ALA-Gel-mediated PDT markedly enhanced reactive oxygen species (ROS) generation and induced potent cytotoxicity in leukoplakia cells, while maintaining high biocompatibility with normal human keratinocytes. In a rat OLK model, the hydrogel achieved prolonged intraoral retention. Upon laser irradiation (632 nm, 100 mW cm−2, 100 J cm−2), both clinical and histopathological assessments confirmed a significant suppression of malignant progression. Furthermore, preliminary clinical trials (n = 30) demonstrated superior therapeutic outcomes compared to conventional treatments. Collectively, this hydrogel-based strategy addresses key challenges in oral PDT, offering a viable and translatable option for OLK management.

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•An adhesive hydrogel for sustained 5-aminolevulinic acid delivery in oral leukoplakia PDT.•Hydrogel ensures wet adhesion, efficient ROS, and superior cell kill in vitro and in vivo.•Clinical trial confirms enhanced efficacy and comfort over conventional PDT for oral cancer prevention.

An adhesive hydrogel for sustained 5-aminolevulinic acid delivery in oral leukoplakia PDT.

Hydrogel ensures wet adhesion, efficient ROS, and superior cell kill in vitro and in vivo.

Clinical trial confirms enhanced efficacy and comfort over conventional PDT for oral cancer prevention.