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Radioprotection in mice following oral administration of WR-1065/PLGA nanoparticles
Sarala Pamujula1, Vimal Kishore, Barbara Rider
1College of Pharmacy, Xavier University of Louisiana, New Orleans, LA 70125, USA.
Purpose:
N-(2-mercaptoethyl)1,3-diaminopropane (WR-1065), is the active metabolite of amifostine, a broad spectrum cytoprotective agent used in conjunction with both chemo- and radiotherapy of certain cancers. This report describes for the first time an oral formulation of WR-1065 and follows on from our earlier report of a similar oral formulation of amifostine.
Materials And Methods:
The nanoparticles of WR-1065 were prepared by spray drying technique using poly lactide-co-glycolide (PLGA) as the polymer matrix. Radioprotection was determined by measuring reductions in radiation-induced: (i) 30-day survival; (ii) bone marrow suppression; and (iii) intestinal injury following 9 Gray (Gy) whole body gamma irradiation in mice. All treatments were given 1 hour pre-irradiation and WR-1065 was tested at the dose of 500 mg/kg.
Results:
The WR-1065/PLGA nanoparticles were smooth and spherical with the average diameter of 206 nm and contained 21.7% (w/w) WR-1065. While irradiation markedly reduced 30-day survival in non-treated control mice, and caused significant bone marrow suppression and intestinal injury in surviving mice, oral administration of WR-1065/PLGA nanoparticles resulted in significant radioprotection as evidenced by a marked reduction in all three of the above mentioned parameters of radiation injury.
Conclusions:
These findings clearly demonstrate the feasibility of developing an effective oral formulation of WR-1065 as a radioprotective agent.
