Rectal delivered nanocomposite suppository against radiation-induced proctitis

Area of Science:

• Biomedical Engineering
• Pharmacology
• Gastroenterology

Background:

• Radiation-induced proctitis is a common radiotherapy side effect with limited treatments.
• Epigallocatechin gallate (EGCG) shows promise but suffers from poor stability and bioavailability.
• Developing stable, locally delivered EGCG formulations is crucial for managing rectal injury.

Purpose of the Study:

• To create a stable, rectally deliverable EGCG formulation for radiation-induced proctitis.
• To enhance EGCG stability and bioavailability using zinc coordination.
• To evaluate the efficacy and safety of the EGCG-zinc formulation in mitigating rectal injury.

Main Methods:

• Preparation of an EGCG-zinc (EGCG-Zn) nanocomplex via metal-polyphenol coordination.
• Formulation of the EGCG-Zn complex into a thermosensitive rectal suppository for sustained release.
• In vivo evaluation in irradiated mouse models assessing oxidative stress, DNA damage, inflammation, and tissue regeneration.

Main Results:

• Zinc coordination enhanced EGCG stability and retained antioxidant activity.
• The thermosensitive suppository provided prolonged rectal residence and increased local drug exposure.
• EGCG-Zn suppositories significantly reduced rectal oxidative stress, DNA damage, and inflammation, while promoting epithelial repair and tight junction restoration in mice.
• No local or systemic toxicity was observed.

Conclusions:

• EGCG-Zn thermosensitive rectal suppositories offer a safe and effective localized treatment for radiation-induced proctitis.
• This formulation demonstrates significant potential for managing radiation-associated rectal injury.
• The study highlights a promising strategy for improving radiotherapy patient outcomes.