Amifostine-Loaded Dissolving Armored Microneedles for Long-Term Prevention of Ionizing Radiation-Induced Injury

Abstract

Amifostine is a cytoprotective agent against ionizing radiation-induced hematopoietic damages although the intravenous injection of amifostine is the unique way and the administration time is strictly restricted. Here we developed an amifostine-loaded dissolving armored microneedle (AAMN) patch with long-term prevention of ionizing radiation-induced injury. Amifostine-loaded hyaluronic acid microneedles (AMNs) were fabricated, dipped in N-vinyl-2-pyrrolidone (NVP) solutions and then UV irradiated to obtain AAMNs. The nail-shaped AAMNs had much higher mechanical strength than the conically shaped AMNs, which was confirmed by in silico simulation. Amifostine rapidly released from AAMNs with 95% of the cumulative release in 60 min at 37 °C due to the dissolving property of AAMNs. The drug cutaneous permeation ability of AAMNs was about two times that of AMNs due to the deeper skin insertion of the former. The controlled drug permeation of AAMNs in the skin and the long-term in vivo drug exposure provided much longer effective protection of the hematopoietic system within 3−7 h administration pre-radiation compared to the merely 0.5-h point of amifostine injection. Survival rates were ensured by AAMNs within the effective time range. Therefore, dissolving AAMNs are a promising transdermal delivery system of amifostine for long-term protection of ionizing radiation-induced injury.