Short chain polyphosphates as a strategic colloidal source of phosphate for parenteral admixtures

Abstract

Short chain sodium polyphosphates – (NaPO3)9 – PolyP – were added to 2-in-1 pediatric parenteral nutrition (PN) formulations as new alternative phosphate sources. Solutions of PolyP and Ca2+ in the presence of Mg2+, glucose, amino acids and trace elements were analyzed by electronic absorption and 31P NMR spectroscopies, as well as by pH measurements. Additionally, to verify the biocompatibility of short chain PolyP solutions, red blood cell (RBCs) units were evaluated by analyzing hemoglobin, hematocrit, and hemolysis. The blood clotting action of the PolyP was determined through Prothrombin time. We observed that the short chain PolyP anions did not interfere in the quality control parameters for RBCs units or in the blood extrinsic coagulation pathway. The spectral changes observed in the 31P NMR confirm the association of Mg2+ and Ca2+ with PolyP in the admixtures. Compatibility diagrams showed that the PolyP-Ca/Mg systems reflect a gel behavior based on the PolyP chains interaction with the incoming cations maintaining a supramolecular equilibrium until a limiting concentration. We observed that the greater the PolyP concentration, the greater the amount of Ca2+ that could be added to the admixture without phase separation and that the increased complexity of species (glucose, amino acid, trace elements and Mg2+) in the admixture favored a still higher final Ca2+ concentration. The overall colloidal behavior of short chain PolyPs shows that these polyanions function not only as alternative and safe phosphate sources in PN formulations but also as polyanions that increase the admixture stability against phase separation by efficiently sequestering metal cations present.