Magnetic semi-permeable polyethyleneimine microcapsules for monitoring of N-nitrosation in the gastrointestinal tract

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Abstract
Semi-permeable polyethyleneimine (PEI) microcapsules were developed recently for trapping unstable electrophilic products in the gastrointestinal tract. Their N-nitrosation has been investigated in vitro and in vivo in the present study. At acid pH N-nitrosation was found to be linearly dependent on nitrite concentration, without a pH maximum. Up to 70% of the nitrosating agent was converted to N-nitroso products that were retained in the microcapsules and detected by a total N-nitroso assay procedure. Microcapsules prepared with different formulations (in order to vary membrane characteristics) provided a limit of detection in the range 1-10 nmol N-nitrosating agent and were also found to have a different capacity for N-nitrosation. Based on n.m.r. data it seems that such N-nitrosation is favoured by the incomplete protonation of this polyamine at acid pH and that nitrosation occurs at the least hindered secondary amine functions. Microcapsules were administered intragastrically in doses of 2 or 6 million to rats also receiving nitrite in the drinking water and were recovered magnetically from faeces. Relative to the maximum possible yield of N-nitrosated microcapsules that could have been excreted within the first 24 h, the excretion (maximum 4.9%) was found to depend on number of capsules administered and the time of administration relative to access to nitrite. Although performed with only a few animals, these preliminary data indicate a performance possibly superior to existing endogenous nitrosation indicators, and a dual purpose system to trap both nitrosating agents and their direct-acting DNA-damaging N-nitroso products.