期刊
ADVANCED SCIENCE
卷 9, 期 15, 页码 -出版社
WILEY
DOI: 10.1002/advs.202200872
关键词
chelation therapy; deferoxamine; hydrogel; iron chelator; sustained release
资金
- NIH/NHLBI [R01HL143020]
- Creative Materials Discovery Program through the National Research Foundation of Korea [2019M3D1A1078938]
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute [H19C1343]
Deferoxamine (DFO) is an FDA-approved iron-chelating agent with good therapeutic efficacy, but its short blood half-life poses challenges for patients who require frequent administrations. By integrating crosslinked hyaluronic acid and Pluronic F127 into an injectable hydrogel formulation, a prolonged release of DFO nanochelators is achieved, significantly extending the half-life and demonstrating potential for the treatment of iron overload disorders.
Deferoxamine (DFO) is an FDA-approved iron-chelating agent which shows good therapeutic efficacy, however, its short blood half-life presents challenges such as the need for repeated injections or continuous infusions. Considering the lifelong need of chelating agents for iron overload patients, a sustained-release formulation that can reduce the number of chelator administrations is essential. Here, injectable hydrogel formulations prepared by integrating crosslinked hyaluronic acid into Pluronic F127 for an extended release of DFO nanochelators are reported. The subcutaneously injected hydrogel shows a thermosensitive sol-gel transition at physiological body temperature and provides a prolonged release of renal clearable nanochelators over 2 weeks, resulting in a half-life 47-fold longer than that of the nanochelator alone. In addition, no chronic toxicity of the nanochelator-loaded hydrogel is confirmed by biochemical and histological analyses. This injectable hydrogel formulation with DFO nanochelators has the potential to be a promising formulation for the treatment of iron overload disorders.
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