Department of Chemistry, National Institute of Technology, Rourkela - 769008, Odisha, India.
Dalton Trans. 2024 Aug 20;53(33):13815-13830. doi: 10.1039/d4dt01839g.
Iron deficiency anaemia (IDA), the most widespread nutritional disorder, is a persistent global health issue affecting millions, especially in resource-limited geographies. Oral iron supplementation is usually the first choice for exogenous iron administration owing to its convenience, effectiveness and low cost. However, commercially available iron supplementations are often associated with oxidative stress, gastrointestinal side effects, infections and solubility issues. Herein, we aim to address these limitations by employing ferritin proteins-self-assembled nanocaged architectures functioning as a soluble cellular iron repository-as a non-toxic and biocompatible alternative. Our studies based on PAGE and TEM indicate that bare ferritin proteins are resistant to gastric conditions but their cage integrity is compromised under longer incubation periods and at higher concentrations of pepsin, which is a critical component of gastric juice. To ensure the safe delivery of encapsulated iron cargo, with minimal cage disintegration/degradation and iron leakage along the gastrointestinal tract, we fabricated the surface of ferritin with chitosan. Further, the stoichiometry and absorptivity of iron-chelator complexes at both gastric and circumneutral pH were estimated using Job's plot. Unlike bipyridyl, deferiprone exhibited pH dependency. kinetics was studied to evaluate iron release from bare and chitosan-fabricated ferritins employing both reductive (in the presence of ascorbate and bipyridyl) and non-reductive (direct chelation by deferiprone) pathways to determine their bio-mineral stabilities. Chitosan-decorated ferritin displayed superior cage integrity and iron retention capability over bare ferritin in simulated gastric fluid. The ability of ferritins to naturally facilitate controlled iron release in conjugation with enteric coating provided by chitosan may mitigate the aforementioned side effects and enhance iron absorption in the intestine. The results of the current study could pave the way for the development of an oral formulation based on ferritin-caged iron bio-mineral that can be a promising alternative for the treatment of IDA, offering better therapeutic outcomes.
缺铁性贫血（IDA）是最常见的营养失调症，是一个持续存在的全球性健康问题，影响着数百万人，尤其是在资源有限的地区。口服铁补充剂由于其方便、有效和低成本，通常是外源性铁给药的首选。然而，市售的铁补充剂常常与氧化应激、胃肠道副作用、感染和溶解度问题有关。在此，我们旨在通过使用铁蛋白蛋白-自组装的纳米笼状结构作为可溶的细胞铁储存库，来解决这些局限性，铁蛋白蛋白作为一种无毒且生物相容的替代品。我们的研究基于 PAGE 和 TEM 表明，裸铁蛋白在胃条件下是稳定的，但在较长的孵育时间和更高浓度的胃蛋白酶下，其笼状结构完整性受到损害，胃蛋白酶是胃液的重要组成部分。为了确保封装的铁货物的安全递送，最小化笼状结构的崩解/降解和铁漏出沿胃肠道，我们用壳聚糖对铁蛋白进行了表面处理。此外，使用 Job 图估计了铁螯合物复合物在胃和近中性 pH 下的化学计量和吸收率。与双吡啶不同，地拉罗司表现出 pH 依赖性。研究动力学以评估裸铁蛋白和壳聚糖制造的铁蛋白中铁的释放，使用还原（存在抗坏血酸和双吡啶）和非还原（直接与地拉罗司螯合）途径，以确定它们的生物矿物稳定性。壳聚糖修饰的铁蛋白在模拟胃液中显示出比裸铁蛋白更高的笼状结构完整性和铁保留能力。铁蛋白自然促进铁的受控释放的能力与壳聚糖提供的肠溶性涂层相结合，可以减轻上述副作用，并增强铁在肠道中的吸收。本研究的结果可能为基于铁蛋白笼状铁生物矿物的口服制剂的开发铺平道路，这种制剂可能是治疗 IDA 的一种有前途的替代方法，提供更好的治疗效果。
