Sucrosomial® Iron: A New Generation Iron for Improving Oral Supplementation

Susana Gómez-Ramírez, Elisa Brilli, Germano Tarantino, Manuel Muñoz, Susana Gómez-Ramírez, Elisa Brilli, Germano Tarantino, Manuel Muñoz

Abstract

Iron deficiency (ID) is usually treated with oral iron salts, but up to 50% of patients complain of gastrointestinal side effects, leading to reduced treatment compliance. Intravenous (IV) iron formulations are increasingly safer, but there is still a risk of infusion and hypersensitivity reactions and the need for a venous access and infusion monitoring. Sucrosomial® iron (SI) is an innovative oral iron formulation in which ferric pyrophosphate is protected by a phospholipid bilayer plus a sucrester matrix (sucrosome), which is absorbed through para-cellular and trans-cellular routes (M cells). This confers SI unique structural, physicochemical and pharmacokinetic characteristics, together with high iron bioavailability and excellent gastrointestinal tolerance. The analysis of available evidence supports oral SI iron as a valid option for ID treatment, which is more efficacious and better tolerated than oral iron salts. SI has also demonstrated similar effectiveness, with lower risks, in patients usually receiving IV iron (e.g., chronic kidney disease, cancer, bariatric surgery). Thus, oral SI emerges as a most valuable first option for treating ID, even more for subjects with intolerance to or inefficacy of iron salts. Moreover, SI should be also considered as an alternative to IV iron for initial and/or maintenance treatment in different patient populations.

Keywords: M cells; Sucrosomial® iron; anemia; bioavailability; efficacy; intravenous iron; iron deficiency; oral iron salts; tolerability.

Conflict of interest statement

S.G.-R. has nothing to declare; E.B. is an Alesco S.r.l. employee; G.T. is a Pharmanutra S.p.A. employee; M.M. has received industry-supplied honoraria for consultancies, lectures and/or travel support from Pharmacosmos, Vifor Pharma, Zambon, Pharmanutra, Sandoz and Celgene, and is member of the editorial board of the journals “Revista Española de Anestesiología y Reanimación”, “Medicina Intensiva” and “Blood Transfusion”.

Figures

Figure 1
Figure 1
Prevalence of iron deficiency across pathologies. (Data taken from references [5,6,7,8,9,10,11,12,13]).
Figure 2
Figure 2
Laboratory assessment of iron status. * Low reticulocyte Hb content (5%) or high soluble transferrin receptor to log ferritin ratio (>2) could identify a component of an absolute iron deficiency in the presence of an inflammation-induced high ferritin level.
Figure 3
Figure 3
Schematic structure of Sucrosomial® iron.
Figure 4
Figure 4
Gastro-resistance and intestinal absorption of Sucrosomial® iron. (A) Gastro-resistant properties of Sucrosomial® iron compared to a sucrester-free iron preparation in an in-vitro simulated gastric fluid digestion at pH 1.2. (B) The involvement of M cells in Sucrosomial® iron uptake was evaluated using an in vitro CACO2/RajiB co-culture. The iron to protein ratio was significantly increased in co-culture cells treated with Sucrosomial® iron (SI), compared to other oral iron formulations: ferrous sulfate (FS), ferrous ascorbate (FeASC), ferrous ethylene-diamine-tetra-acetate (FeEDTA), ferrous bisglycinate (FeBIS), and control (no iron) (data are mean ± SEM, * p < 0.05) (Adapted from references [41,42]).
Figure 5
Figure 5
Bioavailability experiments on CACO-2 cells. Ferritin expression by cells treated with Sucrosomial® iron (SI) was significantly increased, compared to cells treated with ferrous sulfate (FS), phospholipid containing ferric pyrophosphate (Lipofer®), or micronized, dispersible ferric pyrophosphate (SunActive®) (A) or different iron salts, FS, ferric pyrophosphate (FePYR), ferrous ascorbate (FeASC), ferrous ethylene-diamine-tetra-acetate (FeEDTA), ferrous bisglycinate (FeBIS), and control (no iron) (B) (Data are mean ± SEM, * p < 0.001 SI vs. other iron compounds) (Adapted from references [41,45]).
Figure 6
Figure 6
Iron supplementation in anemic piglets and mice. (A) Hemoglobin concentration in anemic piglets treated with iron dextran (FeDEX) or Sucrosomial® iron (SI) (Data are mean ± SD; * p < 0.001, treatment vs. anemic; ** p < 0.001, SI vs. FeDEX). (B) Change in hemoglobin levels in anemic mice after a 14-day treatment with Sucrosomial® iron (SI) or ferrous sulfate (FS). (Data are mean ± SD; * p < 0.01, SI or FS vs. saline; ** p < 0.05, FS vs. vehicle) (Adapted from references [46,47]).
Figure 7
Figure 7
Comparative efficacy of different oral iron formulations for treating bleeding-induced moderate-to-severe anemia. SunActive®, micronized ferric pyrophosphate. Each oral iron formulation was tested in 60 patients (Data taken from reference [89]).

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