BIOMEDICAL (APPLIED/EXPLORATORY)

输血相关铁超载是多种输血依赖性贫血（包括镰状细胞性贫血和重度地中海贫血）患者发病和死亡的主要原因。地铁胺（DFO）是目前铁螯合治疗的“金标准”，已经使用了40多年。问题包括患者的不依从性，快速过滤进入尿液的现象，使给药剂量达到克水平。

Transfusion-related iron overload is a major cause of morbidity and mortality in patients with a variety of transfusion- dependant anemias, including sickle cell anemia and thalassemia major. Desferrioxamine (DFO), the current "gold standard" in iron chelation therapy, has been used for over 40 years. Problems include patient non-compliance the phenomenon of rapid filtration into the urine establishing the administered dosage to gram levels. The aim of this proposal is the development of new, more effective formulations of DFO by allowing entrapment of DFO in tissue-targeted liposomes with prolonged circulation times (i.e. pegylated). This will result in a more effective iron chelation using significantly lower DFO dosage. The novel pegylated formulation (peg-LDFO) will undergo complete biodistribution studies, as well as animal test comparisons with free DFO. The optimal formulation developed during Phase 1 will result in a new drug that eventually will significantly reduce patient iron overload, eliminate the need for pump delivery, reduce treatment cost, and increase patient compliance. Phase II will finalize the formulation in preparation for clinical studies. This therapy applies to a category of orphan diseases which typically afflict impoverished and disenfranchised populations; therefore, commercial opportunity is global.