An extended-release formulation of desferrioxamine for subcutaneous administration

Abstract

Desferrioxamine mesylate (DFO) remains the first line iron chelating agent. Since it has a short half-life and poor absorption through the gastrointestinal tract, DFO must be administered parenterally, usually by daily subcutaneous infusion administered over 8–12 h. The objective of this paper was the development of multivesicular liposome (depofoam) for the extended-release of DFO and study of iron excretion efficiency compared to the free form of DFO. Depofoam particles were characterized by their morphology, particle size, capture volume, and in vitro release. Also, in vivo activity of this formulation in iron overload rats was studied. The in vitro studies in 0.9% sodium chloride at 37°C showed that the multivesicular liposomes released DFO slowly over several days without a rapid initial release, and 57% of DFO was released in 9 days. Administration of a single dose of 100 mg/kg of an optimized Depo-DFO formulation in an iron overload rats, as a single bolus subcutaneous injection, led to significant elevation of urinary iron excretion at the first day that were maintained at levels of more than 110 μg/kg for 3 days. Administration of the unencapsulated DFO at the same dose resulted in elevation of urinary iron excretion in the first day (~73% amount of iron excretion by Depo-DFO) followed by a quick decline to base line levels in the second day. The total urinary iron excreted by Depo-DFO is 3-times greater than that elicited by DFO. In conclusion, Depo-DFO appears to have potential usefulness as an extended-release formulation of DFO.