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Radioprotection, pharmacokinetic and behavioural studies in mouse implanted with biodegradable drug (amifostine)
V Srinivasan1, J A Pendergrass, K S Kumar
1Radiation Casualty Management Team, Radiation Medicine Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA. srinivasan@afrri.usuhs.mil
Biodegradable amifostine implants effectively protected mice against radiation. This sustained drug delivery system showed promising radioprotection, comparable to conventional methods, with improved pharmacokinetics.
Area of Science:
- Pharmacology
- Radioprotection
- Drug Delivery Systems
Background:
- Amifostine is a radioprotective agent.
- Conventional subcutaneous administration of amifostine results in a rapid peak drug concentration.
- Biodegradable implants offer a potential alternative for sustained drug delivery.
Purpose of the Study:
- To evaluate a biodegradable, subcutaneously implantable pellet as a drug delivery system for the radioprotector amifostine.
- To assess the efficacy of amifostine implants in protecting mice against gamma radiation.
Main Methods:
- Mice were subcutaneously implanted with amifostine or placebo pellets.
- Animals were exposed to cobalt-60 gamma radiation at doses ranging from 7-16 Gy.
- Survival rates, pharmacokinetics, and behavioral tests were monitored.
Main Results:
- Amifostine implants provided significant radioprotection (85-95% survival at 10 Gy).
- The LD50/30 was significantly increased in amifostine pellet groups (DRF=1.79).
- Sustained blood WR-1065 levels were observed, unlike the sharp peak with subcutaneous administration.
Conclusions:
- Biodegradable amifostine implants are effective radioprotectors.
- Implantation offers comparable radioprotection to conventional subcutaneous administration.
- Further formulation improvements are needed, but implantation shows pharmacokinetic benefits.
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