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Mucoadhesive Nanothalidomide Enema: Simultaneous Radioprotection and Barrier Repair in Radiation Enteritis Therapy.

Shilong Shao1, Fan Dai1, Qixuan Dai1

  • 1State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.

ACS Nano
|June 3, 2026
PubMed
Summary

A novel nanomedicine formulation of thalidomide (THA) offers targeted rectal delivery for radiation enteritis. This localized therapy protects against radiation damage and repairs the intestinal barrier, improving survival rates.

Keywords:
Carrier-free nanoparticlesDrug deliveryRadiation enteritisRadioprotectionThalidomide

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Important Endpoints and Proliferative Markers to Assess Small Intestinal Injury and Adaptation using a Mouse Model of Chemotherapy-Induced Mucositis

Published on: May 12, 2019

Area of Science:

  • Nanomedicine
  • Gastroenterology
  • Radiotherapy

Background:

  • Radiation enteritis is a severe complication of abdominopelvic radiotherapy with no targeted treatments.
  • Thalidomide (THA) shows anti-inflammatory potential but suffers from poor solubility and delivery challenges.

Purpose of the Study:

  • To develop a targeted nanotherapeutic delivery system for thalidomide to treat radiation enteritis.
  • To evaluate the efficacy and safety of carrier-free THA nanoparticles (Nano THA) in a hyaluronic acid (HA) enema (Nano THA&HA) for localized rectal delivery.

Main Methods:

  • Developed carrier-free THA nanoparticles (Nano THA) using Superstable Pure-nanomedicine Formulation Technology (SPFT).
  • Formulated Nano THA into a hyaluronic acid (HA)-based rectal enema (Nano THA&HA) for enhanced mucoadhesion and sustained release.
  • Evaluated the Nano THA&HA enema in a radiation enteritis model, assessing radioprotection, mucosal repair, and clinical outcomes.

Main Results:

  • Nano THA&HA demonstrated a dual protection mechanism: direct radioprotection (mitigating DNA damage, apoptosis) and active mucosal repair (upregulating tight junctions, activating Nrf2/HO-1 pathway, preserving Lgr5+ stem cells).
  • The treatment ameliorated clinical symptoms, reduced intestinal fibrosis, and significantly increased survival rates in the radiation enteritis model.
  • Localized delivery minimized systemic exposure to THA.

Conclusions:

  • This localized nanotherapeutic strategy using Nano THA&HA is a safe and effective treatment for radiation enteritis.
  • The formulation shows strong potential for managing radiotherapy-induced gastrointestinal toxicity.