Sucrosomial® iron absorption studied by in vitro and ex-vivo models

Abstract

This paper presents a comparative evaluation of different oral ferric iron formulations for ability to retain Fe3+ in simulated gastric fluid (SGF), be internalized by cells lining intestinal epithelium, and cross it to reach the bloodstream. In all formulations iron was ferric pyrophosphate, the excipients were different types and fractions of lecithin plus sucrose esters of fatty acids matrix (Sideral® RM; PRT1; PRT2) or lecithin without sucrester (SUN). Dissolution kinetics of formulations in SGF was studied by USP method. The ability of the formulations to promote iron intestinal absorption was evaluated by the Caco-2 cell model, measuring cellular ferritin content, and by the excised rat intestine model, yielding apparent permeability parameters (Papp). All formulations limited iron release in SGF to ≤10%. Sideral® RM was by far the most absorbed by Caco-2, as ferritin content was in the order: Sideral® RM≫PRT2>PRT1>SUN>control. The Fe3+ crossing the intestinal barrier was in part reduced to Fe2+ by epithelial enzymes, in part it was carried by formulation rearrangement into nano-structures able to protect it from reduction and apt for internalization by epithelium cells. Papp parameters were in the order: Sideral® RM≫PRT1>PRT2>SUN=control. Relevance of transepithelial Fe2+carrier, DMT-1, to Fe3+ transport was ruled out using a DMT-1 inhibitor. In conclusion, Sideral® RM retains iron in SGF, and is the most suitable for Fe3+ internalization by Caco-2 cells, Fe3+ protection from enzymatic reduction and promotion of Fe3+ absorption across intestinal epithelium, non-mediated by DMT-1.