Fabrication of Bletilla Striata polysaccharide-Fe (III) complex and its anti-iron deficiency anemia effects

Iron deficiency anemia (IDA) is one of the most common and widespread forms of anemia, particularly affecting women during pregnancy and postpartum period. Traditional iron supplements primarily consist of inorganic iron, which is often associated with gastrointestinal side effects. In contrast, natural polysaccharide-based iron supplements are gaining popularity owing to their superior absorption, higher bioavailability, and improved biosafety profiles. Conventional methods for synthesizing polysaccharide‑iron complexes typically use sodium hydroxide (NaOH) to regulate the pH of the reaction system. However, NaOH was prone to reacting with carbon dioxide (CO₂) in the air, leading to pH instability and, consequently, fluctuations in the iron content of the final product. Therefore, enhancing the iron content remains a significant challenge. Sodium bicarbonate (NaHCO₃), being alkaline and better stability compared to NaOH, presents a promising alternative. Consequently, we explored the synthesis of a novel polysaccharide‑iron complex using NaHCO₃ as a pH adjusting agent in this study. To address this issue of low iron content, we synthesized a cost-effective and safe Bletilla Striata polysaccharide (BSP) Fe (III) complex under alkaline conditions using an optimized fluidization additive method, with NaHCO₃ as the pH regulator. The BSP-Fe (III) complex was thoroughly characterized via FT-IR, ¹H NMR, XRD, SEM, DSC and TGA. The absorption properties of BSP-Fe (III) in the small intestine were investigated in vitro, along with its effects on IDA mice in vivo. Under optimized conditions-including 2 M FeCl₃, 10 % NaHCO₃, a BSP-to‑sodium citrate mass ratio of 1.3:1, a pH of 9.2, a reaction temperature of 81 °C, and a reaction time of 1.3 h-the BSP-Fe (III) achieved an iron content of 21.12 %, as determined by the Box-Behnken design plus response surface methodology (RSM). The complex was efficiently absorbed in duodenum and jejunum and demonstrated a significant ability to replenish blood in IDA mice. These findings highlighted that NaHCO₃ can effectively replace NaOH as a pH adjuster, successfully enhancing the iron content of BSP-Fe (III) complex from 14.63 % to 21.12 %. This study provides insights that may guide future researches aimed at improving the iron content of polysaccharide-Fe (III) complexes. Furthermore, our BSP-Fe (III) complex exhibited great potential as a safe and non-toxic novel iron supplement, providing a pharmacodynamic foundation for the development of polysaccharide‑iron dosage forms.