Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators.
Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators.
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DOI：
10.1002/advs.202200872
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发表时间：
2022-05
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去铁胺（DFO）是一种FDA批准的铁螯合剂，具有良好的治疗效果，然而，其较短的血液半衰期带来了挑战，例如需要重复注射或连续输注。考虑到铁超载患者对螯合剂的终身需求，可以减少螯合剂给药次数的缓释制剂至关重要。在此，报道了通过将交联的透明质酸整合到Pluronic F127中以延长DFO纳米螯合剂的释放而制备的可注射水凝胶制剂。皮下注射的水凝胶在生理体温下显示出热敏性溶胶-凝胶转变，并在2周内提供肾可清除纳米螯合剂的延长释放，导致半衰期比单独的纳米螯合剂长47倍。此外，通过生物化学和组织学分析证实了负载纳米螯合剂的水凝胶无慢性毒性。这种具有DFO纳米螯合剂的可注射水凝胶制剂具有成为用于治疗铁超负荷病症的有前景的制剂的潜力。通过将交联的透明质酸整合到Pluronic F127中制备的可注射水凝胶制剂显示出在体温下的热敏性溶胶-凝胶转变，并提供了超过2周的肾可清除铁纳米螯合剂的延长释放，导致半衰期比单独的纳米螯合剂长47倍。
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. Injectable hydrogel formulation prepared by integrating crosslinked hyaluronic acid into Pluronic F127 shows a thermosensitive sol–gel transition at body temperature and provides a prolonged release of renal clearable iron nanochelators over 2 weeks, resulting in a half‐life 47‐fold longer than that of the nanochelator alone.