Localized Delivery of Amifostine Enhances Salivary Gland Radioprotection

Area of Science:

• Oncology
• Pharmacology
• Regenerative Medicine

Background:

• Radiotherapy for head and neck cancers often causes xerostomia (dry mouth) due to salivary gland damage.
• Amifostine is the sole FDA-approved drug for preventing xerostomia, but systemic use causes severe side effects like hypotension and nausea.

Purpose of the Study:

• To evaluate the efficacy of retroductal delivery of amifostine and its active metabolite WR-1065 for radioprotection of salivary glands.
• To compare the safety and efficacy of localized versus systemic amifostine administration.

Main Methods:

• Murine submandibular glands were treated with retroductal amifostine/WR-1065 before a 15 Gy radiation dose.
• Salivary gland function, acinar cell survival, and saliva secretion were assessed.
• Blood pressure was monitored to evaluate systemic side effects like hypotension.

Main Results:

• Retroductive delivery of amifostine/WR-1065 significantly improved acinar cell survival and maintained gland function.
• In vivo stimulated saliva secretion was significantly higher in retroductal-treated groups compared to irradiated-only and systemically treated groups.
• Localized WR-1065/amifostine delivery significantly attenuated hypotension, unlike intravenous injections.

Conclusions:

• Localized retroductal delivery of amifostine enhances radioprotection at the cellular level in salivary glands.
• This targeted approach mitigates severe side effects associated with systemic amifostine administration.
• Results support developing localized delivery systems for clinical fractionated radiotherapy regimens.