A calcium delivery system fabricated by poly-γ-glutamic acid: Preparation, characterization, and delivery mechanism studies

Calcium has limited bioavailability owing to the formation of calcium phosphate deposits in the gastrointestinal tract. In this study, a polyglutamic acid (PGA)-Ca complex of calcium chelate was prepared using γ-PGA. The binding constant between γ-PGA and calcium was determined to be 6.50 ± 2.47 × 10⁴ mol/L, where 3.6 units of glutamate was capable of binding one Ca²⁺. The structure of PGA-Ca was characterized, revealing that Ca²⁺ chelation promoted the aggregation of γ-PGA molecules, disrupting the network structure and forming a mineralized β-sheet-rich structure. In vitro digestion experiments demonstrated that PGA-Ca better maintained the soluble state of Ca²⁺ in the intestine compared with CaCl₂. Cell absorption experiments showed that PGA-Ca exhibited 20% higher permeability through Caco-2 cell monolayers than CaCl₂, indicating its higher bioavailability. Notably, PGA-Ca demonstrated improved absorption in the presence of dietary inhibitors, such as oxalate, tannin, and phytate, which compete with Ca²⁺. Finally, the molecular mechanism underlying the promotion of calcium absorption by PGA-Ca was investigated using RNA sequencing. The results reveal that PGA-Ca enhanced Ca²⁺ active transport by upregulating CACNA2D3 and downregulating CBARP, while enhancing paracellular Ca²⁺ transport by downregulating JAM2. This comprehensive study highlights the potential of PGA-Ca as a highly beneficial calcium-delivery system.