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 due 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 – the self-assembled nanocaged architectures functioning as soluble cellular iron repository – as a non-toxic and biocompatible alternative. Our in vitro studies based on PAGE and TEM indicate that bare ferritin proteins are resistant to gastric condition but their cage integrity is compromised under longer incubation periods and at higher concentrations of pepsin, 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 the iron-chelator complexes at both gastric and circumneutral pH was estimated using Job’s plot. Unlike bipyridyl, deferiprone exhibited pH dependency. In vitro kinetics was conducted to evaluate iron release from bare and chitosan-fabricated ferritins employing both reductive (in 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 the enteric coating provided by chitosan may mitigate the aforementioned side effects and enhance iron absorption at the intestine. The results of the current study could pave the way for development of an oral formulation based on ferritin-caged iron bio-mineral that can be a promising alternative towards the treatment of IDA, offering better therapeutic outcomes.

中文翻译：

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裸铁蛋白和壳聚糖制造的铁蛋白及其生物矿物质的胃稳定性：对潜在膳食铁补充剂的影响


缺铁性贫血 (IDA) 是最普遍的营养失调症，是一个持续存在的全球健康问题，影响着数百万人，特别是在资源有限的地区。口服补铁由于其方便、有效且成本低廉，通常是外源性铁剂给药的首选。然而，市售的铁补充剂通常与氧化应激、胃肠道副作用、感染和溶解度问题有关。在这里，我们的目标是通过采用铁蛋白（作为可溶性细胞铁储存库的自组装纳米笼结构）作为无毒且生物相容的替代品来解决这些限制。我们基于 PAGE 和 TEM 的体外研究表明，裸露的铁蛋白对胃部条件具有抵抗力，但在较长的潜伏期和较高浓度的胃蛋白酶（胃液的关键成分）下，其笼的完整性会受到损害。为了确保封装铁货物的安全输送，同时最大限度地减少笼子分解/降解和铁沿胃肠道的渗漏，我们用壳聚糖制造了铁蛋白表面。此外，使用乔布图估计了铁螯合剂复合物在胃和中性周围 pH 值下的化学计量和吸收率。与联吡啶不同，去铁酮表现出 pH 依赖性。采用还原（抗坏血酸和联吡啶存在）和非还原（去铁酮直接螯合）途径进行体外动力学评估裸铁蛋白和壳聚糖制造的铁蛋白的铁释放，以确定其生物矿物质稳定性。在模拟胃液中，壳聚糖修饰的铁蛋白比裸铁蛋白表现出优异的笼完整性和铁保留能力。 铁蛋白与壳聚糖提供的肠溶衣结合自然促进受控铁释放的能力可以减轻上述副作用并增强肠道的铁吸收。目前的研究结果可能为开发基于铁蛋白笼铁生物矿物质的口服制剂铺平道路，该制剂可能成为 IDA 治疗的有希望的替代方案，提供更好的治疗效果。