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Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans.

Pereira DI, Bruggraber SF, Faria N, Poots LK, Tagmount MA, Aslam MF, Frazer DM, Vulpe CD, Anderson GJ, Powell JJ - Nanomedicine (2014)

Bottom Line: We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents.Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota.Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom. Electronic address: dora.pereira@mrc-hnr.cam.ac.uk.

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Absorption of iron from nano Fe(III) in iron-deficient women. (A) Relative bioavailability values (RBV) in relation to Fe(II) sulfate (100%). Percentage RBV for the nano Fe(III) preparations was calculated from the incorporation of labelled 58Fe into red blood cells, as measured by ICP-MS 14 days after ingestion of a single-dose of labelled compound (60 mg elemental Fe). Absorption from Fe(II) sulfate was estimated from the serum Fe curve with validated algorithms.39,66 Nano Fe(III) (a)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (b)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:1:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (c)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:6:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (d)— ligands are gluconic (G) and adipic (A) acids at a ratio 1:1:2 (G:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (e)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was used as a colloidal suspension (i.e. as synthesised) without drying (more details in Table 1). Controls are unmodified Fe(III) oxo-hydroxide (Fe(III)(OH)3) and an ‘unformulated’ mixture of Fe(III) chloride, tartaric acid and adipic acid in the same ratios as those used in nano Fe(III) (a). Box and whisker plots show median, minimum and maximum for n = 2 (Fe(III) (OH)3) or n = 4 (all other iron materials). **, P = 0.004. (B) Pearson's correlation between cellular iron levels in Caco-2 cells exposed to nano Fe(III) (preparations a-e) and relative bioavailability values (%RBV) of the same materials, as shown in Figures 1, C and 2, A. Nano Fe(III) (c) (shown in red triangle) was excluded from the correlation parameters presented in the panel (see Results and Discussion). Values are shown as mean ± SD in both the X and Y directions. Data points are labelled with the nano Fe(III) preparation codes (a-e).
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f0015: Absorption of iron from nano Fe(III) in iron-deficient women. (A) Relative bioavailability values (RBV) in relation to Fe(II) sulfate (100%). Percentage RBV for the nano Fe(III) preparations was calculated from the incorporation of labelled 58Fe into red blood cells, as measured by ICP-MS 14 days after ingestion of a single-dose of labelled compound (60 mg elemental Fe). Absorption from Fe(II) sulfate was estimated from the serum Fe curve with validated algorithms.39,66 Nano Fe(III) (a)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (b)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:1:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (c)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:6:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (d)— ligands are gluconic (G) and adipic (A) acids at a ratio 1:1:2 (G:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (e)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was used as a colloidal suspension (i.e. as synthesised) without drying (more details in Table 1). Controls are unmodified Fe(III) oxo-hydroxide (Fe(III)(OH)3) and an ‘unformulated’ mixture of Fe(III) chloride, tartaric acid and adipic acid in the same ratios as those used in nano Fe(III) (a). Box and whisker plots show median, minimum and maximum for n = 2 (Fe(III) (OH)3) or n = 4 (all other iron materials). **, P = 0.004. (B) Pearson's correlation between cellular iron levels in Caco-2 cells exposed to nano Fe(III) (preparations a-e) and relative bioavailability values (%RBV) of the same materials, as shown in Figures 1, C and 2, A. Nano Fe(III) (c) (shown in red triangle) was excluded from the correlation parameters presented in the panel (see Results and Discussion). Values are shown as mean ± SD in both the X and Y directions. Data points are labelled with the nano Fe(III) preparation codes (a-e).

Mentions: Using the gold standard measurement of isotopic incorporation into haemoglobin we confirmed that, as previously reported in human and rodent feeding studies,23,37,38 Fe(III) oxo-hydroxide that had not been ligand-modified (i.e. unmodified synthetic ferrihydrite) was poorly absorbed/utilised in iron deficient subjects [P < 0.0001 versus Fe(II) sulfate]. Its bioavailability was 5-fold lower than the average of the ligand-modified nano Fe(III) materials (Figure 2, A).


Nanoparticulate iron(III) oxo-hydroxide delivers safe iron that is well absorbed and utilised in humans.

Pereira DI, Bruggraber SF, Faria N, Poots LK, Tagmount MA, Aslam MF, Frazer DM, Vulpe CD, Anderson GJ, Powell JJ - Nanomedicine (2014)

Absorption of iron from nano Fe(III) in iron-deficient women. (A) Relative bioavailability values (RBV) in relation to Fe(II) sulfate (100%). Percentage RBV for the nano Fe(III) preparations was calculated from the incorporation of labelled 58Fe into red blood cells, as measured by ICP-MS 14 days after ingestion of a single-dose of labelled compound (60 mg elemental Fe). Absorption from Fe(II) sulfate was estimated from the serum Fe curve with validated algorithms.39,66 Nano Fe(III) (a)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (b)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:1:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (c)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:6:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (d)— ligands are gluconic (G) and adipic (A) acids at a ratio 1:1:2 (G:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (e)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was used as a colloidal suspension (i.e. as synthesised) without drying (more details in Table 1). Controls are unmodified Fe(III) oxo-hydroxide (Fe(III)(OH)3) and an ‘unformulated’ mixture of Fe(III) chloride, tartaric acid and adipic acid in the same ratios as those used in nano Fe(III) (a). Box and whisker plots show median, minimum and maximum for n = 2 (Fe(III) (OH)3) or n = 4 (all other iron materials). **, P = 0.004. (B) Pearson's correlation between cellular iron levels in Caco-2 cells exposed to nano Fe(III) (preparations a-e) and relative bioavailability values (%RBV) of the same materials, as shown in Figures 1, C and 2, A. Nano Fe(III) (c) (shown in red triangle) was excluded from the correlation parameters presented in the panel (see Results and Discussion). Values are shown as mean ± SD in both the X and Y directions. Data points are labelled with the nano Fe(III) preparation codes (a-e).
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f0015: Absorption of iron from nano Fe(III) in iron-deficient women. (A) Relative bioavailability values (RBV) in relation to Fe(II) sulfate (100%). Percentage RBV for the nano Fe(III) preparations was calculated from the incorporation of labelled 58Fe into red blood cells, as measured by ICP-MS 14 days after ingestion of a single-dose of labelled compound (60 mg elemental Fe). Absorption from Fe(II) sulfate was estimated from the serum Fe curve with validated algorithms.39,66 Nano Fe(III) (a)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (b)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:1:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (c)—ligands are tartaric (T) and succinic (S) acids at a ratio 1:6:2 (T:S:Fe) and the material was dried prior to re-suspension; nano Fe(III) (d)— ligands are gluconic (G) and adipic (A) acids at a ratio 1:1:2 (G:A:Fe) and the material was dried prior to re-suspension; nano Fe(III) (e)—ligands are tartaric (T) and adipic (A) acids at a ratio 1:1:2 (T:A:Fe) and the material was used as a colloidal suspension (i.e. as synthesised) without drying (more details in Table 1). Controls are unmodified Fe(III) oxo-hydroxide (Fe(III)(OH)3) and an ‘unformulated’ mixture of Fe(III) chloride, tartaric acid and adipic acid in the same ratios as those used in nano Fe(III) (a). Box and whisker plots show median, minimum and maximum for n = 2 (Fe(III) (OH)3) or n = 4 (all other iron materials). **, P = 0.004. (B) Pearson's correlation between cellular iron levels in Caco-2 cells exposed to nano Fe(III) (preparations a-e) and relative bioavailability values (%RBV) of the same materials, as shown in Figures 1, C and 2, A. Nano Fe(III) (c) (shown in red triangle) was excluded from the correlation parameters presented in the panel (see Results and Discussion). Values are shown as mean ± SD in both the X and Y directions. Data points are labelled with the nano Fe(III) preparation codes (a-e).
Mentions: Using the gold standard measurement of isotopic incorporation into haemoglobin we confirmed that, as previously reported in human and rodent feeding studies,23,37,38 Fe(III) oxo-hydroxide that had not been ligand-modified (i.e. unmodified synthetic ferrihydrite) was poorly absorbed/utilised in iron deficient subjects [P < 0.0001 versus Fe(II) sulfate]. Its bioavailability was 5-fold lower than the average of the ligand-modified nano Fe(III) materials (Figure 2, A).

Bottom Line: We have developed organic acid-modified Fe(III) oxo-hydroxide nanomaterials, here termed nano Fe(III), as alternative safe iron delivery agents.Furthermore, IHAT did not accumulate in the intestinal mucosa and, unlike Fe(II) sulfate, promoted a beneficial microbiota.Out of the tested preparations, iron hydroxide adipate tartrate met the above criteria, and may become an important tool in addressing this common condition.

View Article: PubMed Central - PubMed

Affiliation: MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom. Electronic address: dora.pereira@mrc-hnr.cam.ac.uk.

Show MeSH
Related in: MedlinePlus