Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Drug Deliv. 2009 Oct;16(7):416-21. doi: 10.1080/10717540903141768.
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 degrees 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 microg/kg for 3 days. Administration of the unencapsulated DFO at the same dose resulted in elevation of urinary iron excretion in the first day (approximately 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.
甲磺酸去铁胺（DFO）仍然是一线铁螯合剂。由于其半衰期短，且在胃肠道吸收不良，DFO必须通过肠胃外途径给药，通常通过每天皮下输注 8-12 小时进行。本文的目的是开发多泡脂质体（depofoam），以延长 DFO 的释放，并研究与游离形式的 DFO 相比，铁排泄效率。depofoam 颗粒的特征在于其形态、粒径、捕获体积和体外释放。此外，还研究了这种配方在铁过载大鼠中的体内活性。在 37°C 的 0.9%氯化钠中的体外研究表明，多泡脂质体在几天内缓慢释放 DFO，没有快速的初始释放，9 天内释放了 57%的 DFO。在铁过载大鼠中单次给予 100mg/kg 优化的 Depo-DFO 制剂，作为单次皮下注射，导致尿铁排泄在第一天显著升高，持续超过 3 天的 110μg/kg 以上水平。以相同剂量给予未包封的 DFO 导致尿铁排泄在第一天升高（Depo-DFO 排泄的铁量约为 73%），然后在第二天迅速降至基线水平。Depo-DFO 排泄的总尿铁量是 DFO 的 3 倍。总之，Depo-DFO 作为 DFO 的延长释放制剂具有潜在的用途。
