Microalgae polyphosphate nanoparticles deliver bioavailable calcium against phytate antagonism: Ex vivo and in vivo...

Biogenic nanoparticles are promising carriers to deliver essential minerals. Here, calcium-enriched polyphosphate nanoparticles (CaPNPs) with a Ca/P molar ratio > 0.5 were produced by Synechococcus sp. PCC 7002 in the growth medium containing 1.08 g/L CaCl₂, and had nearly spherical morphologies with a wide size distribution of 5-75 nm and strongly anionic surface properties with an average ζ-potential of -39 mV, according to dynamic light-scattering analysis, transmission and scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The ex-vivo ligated mouse ileal loop assays found that calcium in CaPNPs was readily available to intestinal absorption via both ion channel-mediated and endocytic pathways, specifically invoking macropinocytic internalization, lysosomal degradation, and transcytosis. Rat oral pharmacokinetics revealed that CaPNPs had a calcium bioavailability approximately 100 % relative to that of CaCl₂ and more than 1.6 times of that of CaCO₃. CaPNPs corrected the retinoic acid-induced increase in serum calcium, phosphorus, and bone-specific alkaline phosphatase, and decrease in serum osteocalcin, bone mineral content/density, and femoral geometric parameters with an efficacy equivalent to CaCl₂ and markedly greater than CaCO₃. In contrast to CaCl₂, CaPNPs possessed desirable resistance against phytate's antagonistic action on calcium absorption in these ex vivo and in vivo studies. Overall, CaPNPs are attractive as a candidate agent for calcium supplementation, especially to populations on high-phytate diets.