Hemin-Loaded Nanoparticles Improve Iron Supplementation and Gut Microbiota Balance in Iron-Deficiency Anemia Therapy

Iron-deficiency anemia (IDA) is a prevalent global health concern, with nonheme iron salts being the most commonly used iron supplementation therapies. However, these therapies are associated with significant side effects and poor efficacy due to interactions with dietary components. Heme iron, which is less susceptible to such interactions, holds promise as an alternative, but suffers from high individual variability in clinical efficacy. This study systematically investigates the biopharmaceutical properties of hemin and identifies its poor solubility and permeability, classifying it as a Class IV drug with low oral bioavailability, which may explain its suboptimal clinical performance. To overcome this limitation, we developed a hemin-loaded nanoparticle formulation (HNP) to enhance the oral bioavailability and therapeutic efficacy of hemin. The formulation is simple to produce, with a high drug loading capacity (30%), and significantly improves the solubility and permeability of hemin. In rats, the HNP increased the relative bioavailability of hemin by 6.5 times. In vivo studies in an IDA mouse model demonstrated that HNP effectively improved anemia-related indicators, such as the red blood cell count, hemoglobin levels, and hematocrit while also alleviating gastrointestinal inflammation. Additionally, HNP administration restored the diversity and abundance of gut microbiota, which is often impaired in IDA. With excellent safety and biocompatibility, HNP represents a promising oral formulation for the treatment of IDA, offering a potential strategy to enhance heme iron bioavailability and reduce individual variability in therapeutic outcomes.