Academic literature on the topic 'Sucrosomial iron'

Sucrosomial® Iron is a recently developed formulation to treat iron deficiency based on ferric pyrophosphate covered by a matrix of phospholipids plus sucrose esters of fatty acids. Previous data indicated that Sucrosomial® Iron is efficiently absorbed by iron-deficient subjects, even at low dosage, and without side effects. Its structural properties may suggest that it is absorbed by an intestinal pathway which is different to the one used by ionic iron. Although, studies in vitro showed that Sucrosomial® Iron is readily absorbed, no animal models have been established to study this important aspect. To this aim, we induced iron deficient anemia in mice by feeding them with a low-iron diet, and then we treated them with either Sucrosomial® Iron or sulfate iron by gavage for up to two weeks. Both iron formulations corrected anemia and restored iron stores in a two-week period, but with different kinetics. Ferrous Sulfate was more efficient during the first week and Sucrosomial® Iron in the second week. Of note, when given at the same concentrations, Ferrous Sulfate induced the expression of hepcidin and four different inflammatory markers (Socs3, Saa1, IL6 and CRP), while Sucrosomial® Iron did not. We conclude that anemic mice are interesting models to study the absorption of oral iron, and that Sucrosomial® Iron is to be preferred over Ferrous Sulfate because of similar absorption but without inducing an inflammatory response.

Abstract Introduction: Proteins such as Ferritin (Ft), Hemoglobin (Hb) and Transferrin Receptor (TfR1) are involved in tissue iron distribution while systemiciron metabolism is regulated by Hepcidin. Interleukin-6 (IL-6) release is induced in response to an inflammatory status and enhances Hepcidin expression, as consequence, dietary iron absorption and macrophage iron recycling are inhibited. Anemia of Chronic Disease (ACD) is a form of anemia associated with many different chronic disorders. It is characterized by high hepcidin and CRP or IL-6 expression and low serum iron transferrin concentration while ferritin can be normal or elevated. Oral iron delivery is especially attractive thanks to the ease of administration, but commonly used iron salts are poorly absorbed and ineffective to increase Hb concentration in particular in patients with ACD. We have developed an oral Iron formulation named Sucrosomial® Iron, preparation of ferric pyrophosphate, covered by a phospholipids plus sucrester matrix, with high bioavailability and tolerability, which promotes ferric iron absorption thanks to gastro-resistant and matrix composition properties and showed Hb concentration improvement not inferior to intravenous iron. Objective: to showpre-clinical and clinical evidences of absorption, effectiveness and tolerability of Sucrosomial Iron using in vivo and in vitro models and in patients with ACD too. Methods: To study the effects of oral supplementation on Iron metabolism and inflammatory status, Hb, Ft, TfR1, Socs3 and Hepcidin expression were analyzed. We have supplemented wild-type (wt) and iron deficient (ID) mice, maintained in iron-free diet for 8 weeks, with 1mg/kg/die of Sucrosomial® Iron or Iron Sulfate or Placebo by oral gavage, for 2 weeks. The role of Sucrosomial® Iron on the inflammatory response, was studied in LPS induced HepG2 hepatoma cells. Cells were treated with Sucrosomial® Iron and the levels of hepcidin were assessed 6, 18 and 24 hours after treatment. To show the efficacy and compliance of Sucrosomial® Iron a multi-centric randomized study on 300 patients with ACD were performed. Patients were supplemented with iron sulfate (65 mg o.i.d.), microencapsulated iron, micronized iron, Sucrosomial® Iron, heminic-chelated bisglycinated and iron chelated bisglycinated iron (30 mg t.i.d.). Median Hb value at the beginning was 8.2 g/dl. In group of patients with high CRP value median Hb value was 7.8 g/dl. Results: In mice treated with Sucrosomial® Iron, Hb level mean increase was 4,9 g/dl while TSAT value is not significantly higher than animals treated with Sulfate Iron. Furthermore mice treated with Sucrosomial® Iron showed a preferential accumulation of iron in spleen. Hepcidin and Socs3 mRNA expression was not induced during Sucrosomial® Iron treatment while was up-regulated in mice treated with Iron Sulfate (Figure 1). In vitro experiments on HepG2 LPS-induced cells displayed that treatment with Sucrosomial Iron® is able to reduce hepcidin concentration at different time points (Figure 2). Data from the clinical study showed that Sucrosomial® Iron is well tolerate and effective ACD patients. Only patients treated with Sucrosomial® Iron showed constant increase in Hb concentration over time. In all groups Hb level achieves a plateau phase after three months and ferritin level starts to increase. At three months higher levels of Hb are present in Sucrosomial® Iron (13.2 g/dl), heminic chelated bisglycinated iron (11.7 g/dl), chelated bisglycinated iron (11.3 g/dl) treated patients. In patients with high CRP level (>30 ng/ml) only those receiving Sucrosomial® Iron showed Hb increase from the tenth week and this continue up to the sixth month (Hb 12.5 g/dl) and seems to be correlated to a significantly decrease of CRP (5 mg/L) (Figure 3). Side effects are higher in ferrous sulfate (15/50) and sunactive treated groups (6/60). Conclusions: In summary, results showed that Sucrosomial® Iron treatment could regulate iron homeostasis through an increase in Hb concentration and better tolerability during inflammatory status. These evidences may suggest that this new oral iron formulation behaves differently than other oral iron salts, perhaps due to different absorption pathways. Besides we have observed a decrease in CRP and Hepcidin concentration, these results should be further investigate. Disclosures Brilli: Pharmanutra S.p.A.: Consultancy. Pera: Pharmanutra S.p.A.: Employment. Tarantino: Pharmanutra S.p.A.: Employment.

Introduction: Iron Refractory Iron Deficiency Anemia (IRIDA) is an autosomal recessive iron metabolism disorder caused by mutations in Tmprss6 gene which encodes for Matriptase2 (MT2) that, by activating hemojuvelin (HJV), regulates the production of hepcidin, the master iron regulatory hormone. Altered MT2 cannot suppress hepatic BMP6/SMAD signaling in low iron condition, hence the resulting hepcidin excess blocks dietary iron absorption and cells release, leading to a form of iron deficiency that is typically refractory to oral iron supplementation. IRIDA is characterized by moderate/severe microcytic anemia (Hemoglobin 6-9 g/dL; MCV 45-65 fL); low transferrin saturation (<5%); impaired oral iron absorption and only a transient response to parenteral iron. Nonetheless, the current treatment is mainly based on parenteral iron therapy. A case study on a child with IRIDA showed for the first time the ability of Sucrosomial® Iron, to increase hemoglobin and MCV values over time (Capra et al., 2017). This oral iron formulation is an innovative preparation of ferric pyrophosphate, covered by a phospholipids plus sucrester matrix, with gastro-resistance properties, high bioavailability and tolerability due to alternative absorption pathways as endocytosis and M cells mediated route (Gomez-Ramirez et al., 2018). Moreover, Sucrosomial® Iron has been successfully used to treat iron deficiency in various clinical conditions, including inflammatory bowel diseases (Abbati et al., 2019). To confirm and characterize the ability of Sucrosomial® Iron to increase Hb in IRIDA disease we studied the response to Sucrosomial® Iron in a IRIDA mouse model (Mask) comparing the efficacy of Sucrosomial® Iron and Sulfate Iron at two different doses and in chronic treatment. Aim: to study Sucrosomial® Iron effect in IRIDA using the Tmprss6 knock-out mouse model Material and Methods: m/m homozygous mice (9-weeks old male mice, four mice per experimental group) were kept at iron balance diet and treated with 0.5 or 4 mg/Kg of Ferrous sulfate, Sucrosomial® Iron (patent n° PCT/IB2013/001659 owned by Alesco s.r.l, Italy), or vehicle by gavage for 35 days. Four 9-weeks old m/- male mice per experimental group were daily treated and Hb and Ht were monitored weekly. Mice were sacrificed at the end of treatments; blood, and different organs were collected for analysis. Total RNA was isolated from tissues using TRIzol Reagent (Ambion), cDNA was generated by Reverse transcription (Promega, Milan, Italy) and samples were analyzed for Hepcidin and Socs3 mRNA levels by qRT-PCR using PowerUp SYBR Green Master Mix (Life Technologies). Results: we analyzed the iron status of anemic homozygous Mask mice from 3 to 35 weeks of age by studying serological and tissue iron content. Interestingly only Sucrosomial® Iron (not Ferrous Sulfate), increased hemoglobin level from 11-12 to 13-14 g/dL in the first week with a tendency to increase until the fourth week, when it stabilized at 13 g/dL (Figure 1A-B). Serum iron concentration was higher in the Sucrosomial® Iron treated animals than in those treated with vehicle, while was lower in the Ferrous sulfate treated animals. Similar pattern was observed for spleen iron content that increased in mice treated with Sucrosomial® Iron but not in those receiving Ferrous sulfate. Liver iron concentration did not apparently varied after the treatments, but duodenal iron increased significantly only in the mice treated with the higher dose of Ferrous sulfate (Figure 1 C-F). Interestingly, we found that the mice treated with both doses of Ferrous sulfate, but not those treated with Sucrosomial® Iron, had a higher mRNA levels of hepcidin and of the inflammatory marker Socs3 (Figure 1 G-H). Conclusion: this study showed for the first time that Sucrosomial® Iron is able to increase hemoglobin level in a mouse model of IRIDA, probably due to its alternative absorption pathway. Sucrosomial® Iron could be used as effective iron supplement to improve iron status in IRIDA patients. Disclosures Girelli: La Jolla Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Vifor Pharma: Other: honoraria for lectures; Silence Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Refractory anaemia (RA) among myelodysplastic syndrome (MDS) is associated with a partial functional iron deficit and may require transfusions. In low-risk lymphoma and solid tumour patients, iron support improves erythropoietin (EPO) cost-effectiveness in treating anaemia. The aim of this study is to see if oral sucrosomial iron support improves the cost-effectiveness of EPO treatment in MDS patients affected by low-risk RA. We treated patients with EPO only or with EPO plus oral sucrosomial iron or intravenous (i.v.) iron. The need for transfusions was lowest in the group taking oral iron (p = 0.016) or not receiving supplementation at all (p = 0.022). We compared costs of EPO with i.v. ferric gluconate or oral sucrosomial iron supplementation or no iron supplementation. The oral iron group had fewer side effects, fewer patient medical visits in the out-patient setting, and fewer transfusions; this led to higher savings on direct hospital costs and indirect patient costs (lost days at work) and translated into a 50% abatement of overall expenditures. EPO treatment-related expenditures in MDS-RA patients were lowest with oral sucrosomial iron supplementation (Sideral®), with a longer interval between EPO administration in maintenance treatment, quicker hemoglobin recovery, lower ferritin increase and fewer blood transfusions.

AbstractIron deficiency is one of the most common nutritional deficiencies worldwide and is often treated with oral iron supplements. However, commonly used supplements, including those based on ferrous iron salts, are associated with gastrointestinal side effects and unfavorable changes in the intestinal microbiome. Sucrosomial® iron is a novel iron formulation that is effective at treating iron deficiency, and with fewer gastrointestinal side effects, yet its effect on the gut microbiome has not been examined previously. Thus, we treated mice for two weeks with diets containing either Sucrosomial® iron or ferrous sulfate as the sole iron source and examined bacterial communities in the intestine using 16S Microbial Profiling of DNA extracted from feces collected both prior to and following dietary treatment. Mice treated with Sucrosomial® iron showed an increase in Shannon diversity over the course of the study. This was associated with a decrease in the abundance of the phylum Proteobacteria, which contains many pathogenic species, and an increase in short chain fatty acid producing bacteria such as Lachnospiraceae, Oscillibacter and Faecalibaculum. None of these changes were observed in mice treated with ferrous sulfate. These results suggest that Sucrosomial® iron may have a beneficial effect on the intestinal microbiome when compared to ferrous sulfate and that this form of iron is a promising alternative to ferrous iron salts for the treatment of iron deficiency.

Abstract Introduction: the involvement of iron in a wide range of metabolic processes make it one of the essential elements for living organisms (Inamura et al., 2005). Anemia of chronic disease (ACD), also termed anemia of chronic inflammation, is the most prevalent anemia in subjects suffering from chronic diseases such as cancer and Chronic Kidney Disease (CKD). A central mechanism by which chronic disease causes anemia is the retention of iron in the reticuloendothelial system, causing a functional iron deficiency and consequently an insufficient iron supply for erythropoiesis. Hepcidin is a primarily liver-derived peptide that orchestrates body iron homeostasis and its expression increases in response to elevated iron stores, inflammation and ER stress (Maliken et al. 2011). In those conditions produced Hepcidin bind to the cellular iron exporter, Ferroportin (Fp1), resulting in Fp1 internalization and degradation with subsequent reduction of cellular iron release (Theurl et al., 2014). Some studies showed that pharmacological inhibition of Hepcidin could reverse cellular iron retetion and improve anemia in different models of inflammatory anemia (Steinbicker et al., 2011, Theurl et al., 2011). Moreover recent scientific publications suggest also a role of other dietary supplements in regulating Hepcidin, reducing its concentration and thus increasing circulating iron in blood (Zughaier et al. 2014). Sucrosomial Iron¨ (Sideral¨) is a new and still unique preparation of ferric pyrophosphate, useful for treatment of iron deficiency related anemia. Aim: we have previously performed a clinical study in which we showed that Sucrosomial iron is able to increase Hemoglobin level in CKD patients (Pisani et al., 2014). On the basis of these results we have investigated the role of Sucrosomial Iron¨ in inflammation process. In particular, we studied the capability of Sucrosomial Iron¨ to reduce Hepcidin release in LPS -induced inflammation made in the hepatoma cell line (HepG2). Results: Cells were incubated with LPS, treated with Sucrosomial Iron¨ and then analyzed for Hepcidin production in terms of protein expression at 6 and 24h after treatment with Sucrosomial Iron¨. Results showed that Sucrosomial Iron¨ is able to significantly reduce Hepcidin level both 6 and 24 h after sucrosome treatment compare to others iron formulations (Figure 1A-B). Materilas and Methods: Sucrosomial Iron¨ preparation of ferric pyrophosphate convered by a; LPS: Lipopolysaccharides from Escherichia coli (Sigma-Aldrich); Empty matrix preparation of phospholipids plus sucrose esters of fatty acids. Conclusions: This evidence should be considered as a preliminary investigation on the effect of Sucrosomial Iron¨ on the production of Hepcidin during chronic inflammation. Bibliography Inamura J et al. Upregulation of hepcidin by interleukin-1 in human hepatoma cell lines. Hepatology Research 33 2005 198-205. Maliken BD et al., The Hepcidin Circuits Act: Balancing Iron and Inflammation, Hepatology. 2011 May ; 53(5): 1764-1766; Theurl M et al. Hepcidin as a predictive factor and therapeutic target in erythropoiesis- stimulating agent treatment for anemia of chronic disease in rats Haematologica. 2014 Sep;99(9):1516-24. Epub 2014 Jun 3. Theurl et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood. 2011;118(18): 4977-84. Steinbicker AU et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation Blood. 2011 May 5;117(18):4915-23. doi: 10.1182/blood-2010-10-313064. Epub 2011 Mar 10. Zughaier SM et al. The role of vitamin D in regulating the iron-hepcidin-ferroportin axis in monocytes. J Clin Transl Endocrinol. 2014 Mar 21;1(1):19-25. Pisani et al. Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrol Dial Transplant. 2015 Apr;30(4):645-52. Epub 2014 Nov 13. Figure 1. This graph shows the level of Hepcidin produced by LPS treated HepG2 cells 6 hours after treatment with iron compounds. Figure 1. This graph shows the level of Hepcidin produced by LPS treated HepG2 cells 6 hours after treatment with iron compounds. Figure 2. This graph shows the level of Hepcidin produced by LPS- treated HepG2 cells 24 hours after treatment with iron compounds. Figure 2. This graph shows the level of Hepcidin produced by LPS- treated HepG2 cells 24 hours after treatment with iron compounds. Disclosures Tarantino: Pharmanutra s.p.a.: Employment. Brilli:Pharmanutra s.p.a.: Employment.

Abstract Introduction: Oral iron delivery is attractive due to the ease of administration and is mainly based on immediate release formulations of ferrous iron. Commonly used ferrous iron salts are poorly absorbed. Overcoming gastrointestinal barriers, is a great challenge and there is a need for new absorption and protective enhancers. Iron DeficiencyAnemia (IDA) is a presenting symptom in approximately 40% of patients with Hodgkin's Lymphoma (HL). Usually with hemoglobin (Hb) between 10 and 12 g/dL. When considering oral iron therapy in cancer patients one must take into account the impact of worsening of existing clinical conditions due to oral iron as intolerance and non-compliance. For these reasons, effective management of iron deficiency anemia is mandatory and iron supplementation is often necessary. To avoid constant exposure of intestinal cells to insoluble iron and consequent side effects, we have developed a new oral Iron formulation named Sucrosomial¨ Iron. This oral formulation is an innovative preparation of ferric pyrophosphate, covered by a phospholipids plus sucrester matrix, with high bioavailability and tolerability and has been showed to improve Hb concentration similarly to intravenous iron but without any gastrointestinal side effects. Objective: to showpre-clinical and clinical evidences of the absorption, effectiveness and tolerability of Sucrosomial¨ Iron. Methods: to study the absorption pathway of Sucrosomial¨ Iron, gastro-resistance and permeation experiments have been performed using in vitro simulated gastric pH digestion, and isolate rat intestine ex vivo models, respectively. To show the efficacy and compliance of Sucrosomial¨ Iron (Sideral¨ Forte) in IDA patients with Hodgkin's Lymphoma (HL), 25 patients were retrospective analyzed, (median age, 35 years; range 26 to 44 years). All patients were staged 2B or higher, according to Ann Arbor classification, none of them showed bone marrow infiltration. A continued treatment with oral Sideral¨ Forte (30 mg/die) was performed for the whole period of chemotherapy administration and iron parameters were tested at the end of the planned treatment. Results: In vitro gastro-resistance experiment displays the ability of Sucrosomial¨ Iron (SRM), to avoid release of Ferric Iron from the matrix compared to phospholipid only-containing iron formulation (PCC, Figure 1). These results showed the gastro-resistance features of SRM.We have performed ex-vivo permeability experiments using Hussing chamber-like experimental model and measured ferric iron concentration in presence of bivalent iron chelator (BPDS) too. Thanks to this model we have showed that SRM is able to cross the intestinal tissue through a passive transport in respect to the other iron formulations (Figure 2). Moreover we have observed that Sucrosome components ratio is pivotal for kinetics properties of Sucrosomial¨ Iron. Data from the clinical study showed that Sideral¨ Forte is well tolerated and effective in patients with HL in advanced stage. At baseline (T0) medium Hb level was 10.2 g/dL, median serum iron and total iron-binding capacity (TIBC) were 35 μg/dL and 244 μg/dL respectively. Ferritin levels showed a wide variation with a median of 90 ng/mL. At the end of treatment (T1 6 months) medium Hb level was 12.8 g/dL (+2,2 g/dL) the median serum iron and total iron-binding capacity increased up to 95 μg/dL and 264 μg/dL and Ferritn levels increased with a median of 277 ng/mL (Figure 3). Thanks to the high compliance and tolerability, all patients were able to continue Sucrosomial¨ Iron supplementation up to the end of the chemioterapy period. CONCLUSIONS: these results showed that Sucrosomial technology is able to protect ferric iron from the gastric pH conferring the ability to reach covered the intestine for absorption and to cross intestinal epithelium through a passive route; thus minimizing the conventional oral iron side effects and increasing Hb and Ferritin levels in HL patients. SRM Iron pyrophosphate, Lecithin, Sucrester PCC phospholipid-containing carrier BPDS Bivalent Iron chelator PYR Iron pyrophosphate SLP pyr, Lecithin, low phospholipid concentration, Sucrester SRMS pyr, Lecithin, high Sucrester concentration Results are expressed as median values *p<0,05 Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Brilli: Pharmanutra S.p.A.: Employment. Tarantino:Pharmanutra S.p.A.: Employment.

Abstract Introduction: Iron deficiency is one of the most widespread nutritional deficiencies. Globally two billion people are suffering from iron- deficiency anemia (Hermida et al., 2010). Oral therapy for iron deficiency is mainly based on immediate release formulations of ferrous iron. However, modified formulations have been marketed to reduce gastrointestinal side effects and to prevent iron instability in the gastrointestinal tract. Overcoming biological barriers, including the gastrointestinal epithelial barriers, is a great challenge for pharmaceutical research and thus there is a need for new absorption enhancers with more favorable profile. Sucrose esters are widely used in the food industry, and there are reports on their potential use in pharmaceutical formulations as excipients (Szuts A et al., 2008). In vitro methods using cell cultures have been proposed to assess iron bioavailability as an alternative to in vivo methods. Caco-2 cells have shown numerous morphological and biochemical characteristics of enterocytes and have been successfully used to study iron absorption (Garcia et al., 1996; Jovani et al., 2001). Caco-2 monolayers formed a good barrier as reflected by high transepithelial resistance and positive immunostaining for junctional proteins. Sucrose esters in nontoxic concentrations significantly reduced resistance and impedance, and increased permeability of some components in Caco-2 monolayers. Recent data indicate that sucrose esters can enhance drug permeability through both the transcellular and paracellular routes (Kiss et al., 2014). Aim: The strong correlation between the published human absorption data and the iron uptake by Caco-2 cells makes them an ideal in vitro model to study iron bioavailability (Au and Reddy, 2000). For this, in the present study, we compared the bioavailability of innovative Oral Iron formulation based on Sucrosomial Iron¨ (Sideral¨) with three different Iron formulations (Figure 1). Materials and Methods: Sucrosomial Iron, preparation of ferric pyrophosphate convered by a phospholipids plus sucrose esters of fatty acids matrix; Lipofer¨, a water-dispersible micronised iron; Sunactive¨ ferric pyrophosphate, lecithin and emulsifiers. Results: The data showed that Sucrosomial Iron¨ (Sideral¨), is significantly more bioavaible than microencapsulated Ferric pyrophosphate ingredients, Lipofer¨ and Sunactive¨ and Ferrous Sulfate in Caco-2 cell model (Figure 1). Bibliography Au, A. P., Reddy, M. B. (2000). Caco-2 cells can be used to assess human iron bioavailability from a semipurified meal. J Nutr 130:1329-1334. Garcia et al. (1996). The Caco-2 cell culture system can be used as a model to study food iron availability. J Nutr 126:251-258. Hermida et al., Preparation and characterization of iron-containing liposomes: their effect on soluble iron uptake by Caco-2 cells Journal of Liposome Research, 2010, 1-10, Jovani et al. (2001) Calcium, iron, and zinc uptake from digests of infant formulas by Caco-2 cells. J Agric Food Chem 49:3480-3485. Kiss et al., (2014) Sucrose esters increase drug penetration, but do not inhibit p-glycoprotein in caco-2 intestinal epithelial cells J Pharm Sci. Oct;103(10):3107-19. Szuts A et al. (2008) Study of the effects of drugs on the structures of sucrose esters and the effects of solid-state interactions on drug release J Pharm Biomed Anal. 48: Figure 1. the graph shows the Ferritin levels of Caco-2 cells after iron formulations treatment. Sucrosomial Iron treated cells display significant increase of Ferritin synthesis compared to Lipofer and SunActive treated cells. Figure 1. the graph shows the Ferritin levels of Caco-2 cells after iron formulations treatment. Sucrosomial Iron treated cells display significant increase of Ferritin synthesis compared to Lipofer and SunActive treated cells. Disclosures Tarantino: Pharmanutra s.p.a.: Employment. Brilli:Pharmanutra s.p.a.: Employment.

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.

CKD is diagnosed when there’s a decreased kidney function shown by a GFR less than 60 ml / min (established for a reference man with 1.73 m² body surface area), or markers of kidney damage, or both, of at least 3 months duration. The severity of complications increases in parallel with the GFR decline. We focused on three comorbidities extremely common in CKD patients: oxidative stress and inflammation; anemia and dysbiosis. We investigated these CKD comorbidities both with in vitro and in vivo approaches. More in detail, regarding in vivo studies, we measured oxidative stress biomarkers in a population of ESRD patients before and after the hemodialysis treatment, comparing the results with a population of healthy subjects; we evaluated oxidative stress biomarkers in the plasma of HD patients before, during and after two type of iron treatments (intravenous and sucrosomial iron). Regarding in vitro experiments, we focused on two uremic toxins, urea and indoxyl sulphate, and we evaluated their effects on a human endothelial cell line (Human Microvascular Endothelial Cells 1, HMEC-1).