Rectal delivered nanocomposite suppository against radiation-induced proctitis

BACKGROUND: Radiation-induced proctitis is a common complication of radiotherapy for pelvic malignancies, for which effective local treatments remain limited. Epigallocatechin gallate (EGCG) has antioxidant and anti-inflammatory activities but is limited by poor stability and bioavailability. This study aimed to develop a stable, rectally deliverable EGCG-based formulation to mitigate radiation-induced rectal injury. RESULTS: An EGCG-zinc (EGCG-Zn) nanocomplex was prepared via metal-polyphenol coordination and formulated into a thermosensitive rectal suppository for localized delivery. Zinc coordination significantly improved EGCG stability while preserving its antioxidant activity. The suppository enabled prolonged rectal residence and enhanced local drug exposure. In irradiated mouse models, EGCG-Zn suppositories reduced oxidative stress, DNA damage, and inflammatory responses in rectal tissue, and promoted epithelial regeneration and tight junction restoration. Transcriptomic and molecular analyses suggested involvement of inflammation-related and epithelial barrier-associated signaling pathways. No detectable local or systemic toxicity was observed after repeated administration. CONCLUSIONS: These findings indicate that an EGCG-Zn-based thermosensitive rectal suppository is a safe and effective localized strategy for alleviating radiation-induced proctitis, with potential translational value for the management of radiation-associated rectal injury.