Bioaccessibility and Caco-2 cell uptake of iron chlorophyllin using a biologically relevant digestion model.

Iron deficiency remains a top nutrient deficiency worldwide. Iron chlorophyllin (IC), a compound structurally analogous to heme, utilizes the protoporphyrin ring of chlorophyll to bind iron. IC has previously been shown to deliver more iron to Caco-2 cells than FeSO4, the most common form prescribed for supplementation. However, previous test conditions used digestive conditions outside of those observed in humans. This study sought to assess IC bioaccessibility and Caco-2 cell uptake using physiologically relevant digestive solutions, pH, and incubation time, as compared to other iron sources (i.e., FeSO4, and hemoglobin (Hb)). Co-digestion with ascorbic acid (AA) and albumin was also investigated. Following gastric, duodenal, and jejunal digestion, IC-bound iron was less bioaccessible than iron delivered as FeSO4, and IC-bound iron was less bioaccessible than Hb-bound iron. IC-bound iron bioaccessibility was not affected by AA and was enhanced 2x when co-digested with a low dose of albumin. However, Caco-2 cell incubation with IC-containing digesta increased cell ferritin 2.5x more than FeSO4 alone, and less than Hb. IC with AA or with 400 mg albumin also increased cell ferritin more than IC alone, with the greatest increases observed following incubation of digesta containing IC + AA + 400 mg albumin. These results suggest IC can serve as an improved source of iron for supplementation as compared to FeSO4. These results also support further in vivo investigations of IC-based iron delivery in populations at risk of iron deficiency.

Consumption of a Single Dose of Prebiotic Galacto-Oligosaccharides Does Not Enhance Iron Absorption from Micronutrient Powders in Kenyan Infants: A Stable Iron Isotope Study.

BACKGROUND: Long-term feeding of prebiotic galacto-oligosaccharides (GOS) increases iron absorption in African infants, but the underlying mechanism and how long GOS need to be fed to infants to achieve an increase in absorption is uncertain. OBJECTIVES: In Kenyan infants, we tested whether the addition of GOS to a single test meal would affect iron absorption from a micronutrient powder (MNP) containing ferrous sulfate (FeSO4) and another MNP containing ferrous fumarate (FeFum) and sodium iron ethylenediaminetetraacetate (NaFeEDTA). METHODS: In a randomized-entry, prospective crossover study, iron deficient (87%) and anemic (70%) Kenyan infants (n  = 23; mean ± SD age, 9.9 ± 2.1 months) consumed 4 stable iron isotope-labeled maize porridge meals fortified with MNPs containing 5 mg iron as FeFum + NaFeEDTA, or FeSO4, either without or with 7.5 g GOS. The primary outcome, fractional iron absorption (FIA), was assessed by erythrocyte incorporation of isotopic labels. Data were analyzed using a 2-way repeated-measures ANOVA. RESULTS: There was no significant interaction between GOS and the iron compounds on FIA, and the addition of GOS did not have a significant effect on FIA. There was a statistically significant difference in FIA between the meals fortified with FeSO4 and with FeFum + NaFeEDTA (P  < 0.001).Given with GOS, FIA from FeSO4 was 40% higher than from FeFum + NaFeEDTA (P  < 0.001); given without GOS, it was 51% higher (P  < 0.01). CONCLUSIONS: The addition of GOS to a single iron-fortified maize porridge test meal in Kenyan infants did not significantly increase iron absorption, suggesting long-term feeding of GOS may be needed to enhance iron absorption at this age. This study was registered at clinicaltrials.gov as NCT02666417.

The Efficacy and Safety of Vitamin C for Iron Supplementation in Adult Patients With Iron Deficiency Anemia: A Randomized Clinical Trial.

Importance: It remains uncertain whether vitamin C routinely used with oral iron supplements is essential for patients with iron deficiency anemia (IDA). Objective: To compare the equivalence and assess the safety of oral iron supplements plus vitamin C or oral iron supplements alone in patients with IDA. Design, Setting, and Participants: This single-center, open-label, equivalence randomized clinical trial was conducted from January 1, 2016, to December 30, 2017, in Huashan Hospital, Fudan University. Adult patients with newly diagnosed IDA were enrolled. Participants were randomly assigned (1:1) to the oral iron supplements plus vitamin C group or the oral iron supplements-only group. Data analysis was performed from March to December 2018. Interventions: Patients were randomized to receive a 100-mg oral iron tablet plus 200 mg of vitamin C or a 100-mg iron tablet alone every 8 hours daily for 3 months. Main Outcomes and Measures: The primary outcome was the change in hemoglobin level from baseline to 2 weeks of treatment, and an equivalence margin of 1 g/dL in hemoglobin was chosen for the demonstration of comparable efficacy. Secondary outcomes included the change in the reticulocyte percentage after 2 weeks of treatment, the increase in hemoglobin level after 4 weeks of treatment, the increase in serum ferritin level after 8 weeks of treatment, and adverse events. Results: Among the 440 randomized patients (220 each in the oral iron supplements plus vitamin C group and iron-only group; 426 women [96.8%]; mean [SD] age, 38.3 [11.7] years), all were assessed for the primary outcome, and 432 (98.2%) completed the trial. From baseline to the 2-week follow-up, the mean (SD) change in hemoglobin level was 2.00 (1.08) g/dL in the oral iron supplements plus vitamin C group and 1.84 (0.97) g/dL in the oral iron supplements-only group (between-group difference, 0.16 g/dL; 95% CI, -0.03 to 0.35 g/dL), thus meeting the criteria for equivalence. The mean (SD) change in serum ferritin level from baseline to 8-week follow-up was 35.75 (11.52) ng/mL in the vitamin C plus iron group and 34.48 (9.50) ng/mL in the iron-only group (between-group difference, 1.27 ng/mL; 95% CI, -0.70 to 3.24 ng/mL; P = .21). There were no significant differences between the 2 groups regarding the rates of adverse events (46 [20.9%] vs 45 [20.5%]; difference, 0.4%; 95% CI, -6.7% to 8.5%; P = .82). No patient withdrew because of adverse events. Conclusions and Relevance: Among patients with IDA, oral iron supplements alone were equivalent to oral iron supplements plus vitamin C in improving hemoglobin recovery and iron absorption. These findings suggest that on-demand vitamin C supplements are not essential to take along with oral iron supplements for patients with IDA. Trial Registration: ClinicalTrials.gov Identifier: NCT02631668.

Acute Consumption of Prebiotic Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate, but not from Ferrous Sulfate and Ferric Pyrophosphate: Stable Iron Isotope Studies in Iron-Depleted Young Women.

BACKGROUND: Although acute consumption of high doses of prebiotic galacto-oligosaccharides (GOS) increases fractional iron absorption (FIA) from ferrous fumarate (FeFum), it is uncertain if low doses of GOS have this effect. Furthermore, whether GOS improve iron absorption from other commonly used iron compounds and whether ascorbic acid (AA) enhances the effect of GOS on iron absorption from FeFum is unclear. OBJECTIVES: In iron-depleted women [serum ferritin (SF) <30 µg/L], we assessed: 1) whether the acute enhancing effect of GOS on FeFum is dose dependent; 2) if GOS would affect FIA from ferrous sulfate (FeSO4) or ferric pyrophosphate (FePP); and 3) if AA and GOS given together enhance FIA from FeFum to a greater extent compared with GOS alone. METHODS: We recruited 46 women (mean age 22.0 y, mean BMI 21.3 kg/m2, median SF 17.1 µg/L), and measured FIA from 14 mg iron labeled with stable isotopes in the following conditions: 1) FIA from FeFum given with 3.5 g, 7 g GOS, and without GOS; 2) FIA from FeSO4 and FePP given with and without 15 g GOS; and 3) FIA from FeFum given with 7 g GOS with and without 93 mg AA. FIA was measured as erythrocyte incorporation of stable isotopes after 14 d. Comparisons were made using paired samples t-test or Wilcoxon rank sum test where appropriate. RESULTS: Giving 7 g of GOS significantly increased FIA from FeFum (+26%; P = 0.039), whereas 3.5 g GOS did not (P = 0.130). GOS did not significantly increase FIA from FeSO4 (P = 0.998) or FePP (P = 0.059). FIA from FeFum given with GOS and AA was significantly higher compared with FeFum given with GOS alone (+30%; P <0.001). CONCLUSIONS: In iron-depleted women, GOS does not increase FIA from FeSO4 or FePP, but it increases FIA from FeFum. Thus, a combination of FeFum and GOS may be a well-absorbed formula for iron supplements. The study was registered at clinicaltrials.gov as NCT03762148.

The bioavailability of iron picolinate is comparable to iron sulfate when fortified into a complementary fruit yogurt: a stable iron isotope study in young women.

PURPOSE: A technological gap exists for the iron (Fe) fortification of difficult-to-fortify products, such as wet and acid food products containing polyphenols, with stable and bioavailable Fe. Fe picolinate, a novel food ingredient, was found to be stable over time in this type of matrix. The objective of this study was to measure the Fe bioavailability of Fe picolinate in a complementary fruit yogurt. METHODS: The bioavailability of Fe picolinate was determined using stable iron isotopes in a double blind, randomized cross-over design in non-anemic Swiss women (n = 19; 25.1 ± 4.6 years). Fractional Fe absorption was measured from Fe picolinate (2.5 mg 57Fe per serving in two servings given morning and afternoon) and from Fe sulfate (2.5 mg 54Fe per serving in two servings given morning and afternoon) in a fortified dairy complementary food (i.e. yogurt containing fruits). Fe absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean (95% CI) fractional iron absorption from Fe picolinate and Fe sulfate were not significantly different: 5.2% (3.8-7.2%) and 5.3% (3.8-7.3%) (N.S.), respectively. Relative bioavailability of Fe picolinate versus Fe sulfate was 0.99 (0.85-1.15). CONCLUSION: Therefore, Fe picolinate is a promising compound for the fortification of difficult-to-fortify foods, to help meet Fe requirements of infants, young children and women of childbearing age.

Microencapsulation performance of Fe-peptide complexes and stability monitoring.

Iron supplementation presents several challenges, such as low bioavailability, high reactivity and a metallic taste. Iron absorption is enhanced by complexing with organic compounds such as peptides, while microencapsulation is an alternative to protect the mineral and mask undesirable flavors. Fe-peptide complexes were obtained by reacting small whey peptides (< 5 kDa) with iron (from ferrous sulfate) under controlled conditions. Maltodextrin (MD) and polydextrose (PD) were used as the wall materials and spray dried to form particles containing the active Fe-peptide. The conditions of enzymatic hydrolysis with the bacterial endopeptidase produced from Bacillus licheniformis were optimized to achieve a high degree of cleavage (~20% degree of hydrolysis). The physicochemical and structural properties of the microparticles were evaluated during storage (365 days). The encapsulation process showed high efficiency (84%) and process yield (≥90%). The iron dialyzability and uptake by Caco-2 cells from microparticles were at least 3-fold higher than the ferrous sulfate. The water content and water activity varied from 3.0 to 5.7% and from 0.29 to 0.44, respectively, after 365 days. SEM revealed morphological stability during storage and EDX showed the presence of iron ions at the surface of the microparticles, which could be free or complexed. The microparticles can be an alternative of higher bioavailable iron besides the further protection and iron stability which the microparticles may present when compared with the Fe-peptide complexes. Future studies could demonstrate the feasibility of applying these microparticles in formulation for food supplementation, concerning bioavailability and sensory aspects.

Magnetic nanoparticles-loaded liposomes as a novel treatment agent for iron deficiency anemia: In vivo study.

Iron deficiency anemia (IDA) is a major worldwide public health problem. This is due to its prevalence among infants, children, adolescents, pregnant and reproductive age women. Ferrous sulfate (FeSO4) is the first line therapy for iron IDA. Unfortunately, it is reported that FeSO4 suffers from low absorption rate in the body and itself exhibits severe side effects. Herein, iron oxide magnetic nanoparticles-loaded liposomes (LMNPs) are prepared, characterized and evaluated as a treatment regimen for IDA in Wistar rats (as an animal model). Iron oxide magnetic nanoparticles (MNPs) are prepared and loaded into liposomes using the thin film hydration method. The size of the prepared formulations is in the range 10-100 nm, thus it can avoid the reticular endothelial system (RES), and increased their blood circulation time. For in vivo assessment, thirty-five Wistar rats are divided into 5 groups (n = 7): negative control group, positive control group, and three groups treated with different iron formulations (FeSO4, MNPs and LMNPs). Anemia is induced in the anemic groups by the bleeding method and then treatment started with different iron compounds administrated orally for 13 days. Hematological parameters are followed up during the treatment period. Results indicate that, in the LMNPs group, the hematological parameters turn to normal values and the histopathological structures of the liver, spleen and kidney remain normal. This proves that liposome increases the bioavailability of MNPs. In conclusion, LMNPs demonstrate superiority as a therapeutic regimen for the treatment of IDA among the tested iron formulations.

Feralgine™ a New Approach for Iron Deficiency Anemia in Celiac Patients.

BACKGROUND: Celiac disease (CD) is an immunologically-mediated disorder characterized by duodenal mucosa villi atrophy. Iron absorption is usually reduced in celiac patients making every kind of oral iron treatment unhelpful because of malasorption. Feralgine™ is a new product that has been demonstrated to be more bioavailable. As such, the aim of our study was to evaluate the absorption of Feralgine™ in adult patients with CD. METHODS: Twenty-six adults affected by Iron Deficiency Anemia (IDA), of which 14 were also affected by CD and 12 were not affected by CD, were enrolled. An oral iron absorption test (OIAT) was performed in each patient by administrating Feralgine™, and serum iron was evaluated at baseline (T0) and after 2 h (T1) from the oral iron ingestion. RESULTS: The OIAT was well tolerated in all patients, and, surprisingly, an equivalent statistically significant improvement in serum iron occurred in the two groups of patients (IDA plus CD: T0 = 28.21 µg/dL vs. T1 = 94.14 µg/dL p = 0.004 and IDA without CD: T0 = 34.91 µg/dL vs. T1 = 118.83 µg/dL, p = 0.0003). CONCLUSIONS: These results demonstrated the high absorption of Feralgine™ in celiac patients, confirming our previous data obtained with Ferrous Bysglicinate in children with CD.

Consumption of Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate: A Stable Iron Isotope Study in Iron-Depleted Young Women.

BACKGROUND: Animal studies suggest prebiotics can increase iron absorption, but results from human studies are equivocal. OBJECTIVES: In iron-depleted women, before (baseline) and after daily consumption of galacto-oligosaccharides (GOS) for 4 wk, we sought to assess fractional iron absorption (FIA) from an iron supplement given with and without single doses of GOS in test meals or water. METHODS: In all women (n = 34; median serum ferritin concentration = 16.4 µg/L), FIA from doses of 14 mg iron labeled with stable isotopes was measured in the following conditions at baseline: 1) FIA from ferrous fumarate (FeFum) in water given with and without 15 g GOS; 2) FIA from FeFum in a test meal given with and without 15 g GOS; 3) FIA from ferrous sulfate (FeSO4) in a test meal given without 15 g GOS. All subjects then consumed âˆ¼15 g GOS daily for 4 wk. Then the following conditions were tested: 4) FIA from FeFum in a test meal with and without 15 g GOS; and 5) FIA from FeSO4 in a test meal with 15 g GOS. FIA was measured as erythrocyte incorporation of stable isotopes. RESULTS: At baseline, GOS significantly increased FIA from FeFum when given with water (+61%; P < 0.001) and the meal (+28%; P = 0.002). After 4 wk of GOS consumption, GOS again significantly increased FIA from FeFum in the meal (+29%; P = 0.044). However, compared with baseline, consumption of GOS for 4 wk did not significantly enhance absorption from FeFum in the meal given without GOS. FIA from FeSO4 given with GOS in a meal after 4 wk of GOS consumption was not significantly greater than FIA from FeSO4 in a meal without GOS at baseline. CONCLUSIONS: In iron-depleted women, GOS given with FeFum increases FIA, but 4 wk of GOS consumption did not enhance this effect. The study was registered at clinicaltrials.gov as NCT03325270.

Use of a Probiotic to Enhance Iron Absorption in a Randomized Trial of Pediatric Patients Presenting with Iron Deficiency.

OBJECTIVE: To evaluate the efficacy of low dose ferrous sulfate for the treatment of iron deficiency and if the probiotic Lactobacillus plantarum 299v (LP299v) enhances treatment. STUDY DESIGN: This randomized, double-blinded, controlled trial of the treatment of iron deficiency in children compared the use of low-dose ferrous sulfate (1-3 mg/kg/day), with or without probiotic (LP299v). RESULTS: Serum ferritin level increased in all children from a baseline of 23.7 ng/mL to 45.4 ng/mL after 6-8 weeks of treatment. There was no significant difference in the increase in serum ferritin in children taking the probiotic LP299v compared with controls (23.2 vs 20.0 ng/mL, respectively). Additionally, an increase in ferritin level was not significantly associated with probiotic use when controlling for other factors, including child weight and dosing. Overall, the treatments were well-tolerated, with mild side effects. CONCLUSIONS: Treatment with low-dose ferrous sulfate is well-tolerated and effective in correcting iron deficiency in children. However, the probiotic LP299v did not enhance treatment. Further attention should examine the dose-response effect in children, including an alternate day dosing schedule. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01617044.

Comparison Study of Iron Bioaccessibility from Dietary Supplements and Microencapsulated Preparations.

Iron deficiency is the most common form of malnutrition. Factors responsible for this so-called "hidden hunger" include poor diet, increased micronutrient needs and health problems such as diseases and infections. Body iron status can be increased by the intake of dietary supplements and fortified food. The aim of the present study was to compare iron bioaccessibility from commercial nutritional supplements and iron microcapsules. A comparison study was performed under conditions mimicking gastric and gastrointestinal digestion. A preparation of encapsulated ferrous sulphate or lactate and vitamin C, in a formula, showed bioaccessibility factors of up to 100% when digested individually, and around 60% in the presence of a food matrix. The degree of oxidation of the ferrous ions differed, depending on the type of preparation, the presence of vitamin C and the food matrix. The highest percentage content of ferrous ion, in the soluble fractions after gastrointestinal digestion, was shown by the preparation containing microencapsulated ferrous lactate or ferrous sulphate and vitamin C. Encapsulation seems to limit the interaction of iron with the food matrix and protect it against oxidation, thus making it more accessible for intestinal uptake.

A new ferrous diflunisal complex and its effects on biopools of labile iron.

Drugs bearing metal-coordinating moieties can alter biological metal distribution. In this work, a complex between iron(II) and diflunisal was prepared in the solid state, exhibiting the following composition: [Fe(diflunisal)2(H2O)2], (Fe(dif)2). The ability of diflunisal to alter labile pools of both plasmatic and cellular iron was investigated in this work. We found out that diflunisal does not increase the levels of redox-active iron in plasma of iron overloaded patients. However, diflunisal efficiently carries iron into HeLa or HepG2 cells, inducing an iron-catalyzed oxidative stress.

Oral iron absorption test with ferrous bisglycinate chelate in children with celiac disease.

BACKGROUND: Celiac disease (CD) is an immunologically-mediated enteropathy resulting in small-bowel mucosal villous atrophy with crypt hyperplasia. Iron malabsorption is usually observed in CD. Only few studies investigated oral iron absorption in subjects with gastrointestinal diseases and Iron Deficiency Anemia (IDA), using the oral iron absorption test (OIAT). We considered useful to investigate the OIAT, using ferrous bisglycinate chelate (FBC), in patients with CD at diagnosis or on gluten free diet (GFD) from at least 1 year. METHODS: A total of 25 patients with CD (3-18 years old) and iron depletion, at diagnosis of CD (N.=12) or on GFD from at least 12 months (N.=13), were considered. Serum iron was evaluated at baseline (T0) and after 3 hours (T1) from the oral iron ingestion. Statistical analyses were conducted using SPSS 21.0 software for Mac. RESULTS: OIAT was well tolerated by all patients. An important increase of the serum iron at T1, of at least twice the baseline values, occurred in all patients except in one (P value <0.0005). CONCLUSIONS: These results demonstrated good efficacy of the FBC, not only in patients with CD on GFD but also in children with newly diagnosed CD with the characteristic intestinal lesions.

Ferrocene-based inhibitors of hepatitis C virus replication that target NS5A with low picomolar in vitro antiviral activity.

An unprecedented series of organometallic HCV (hepatitis C virus) NS5A (nonstructural 5A protein) replication complex inhibitors that incorporates a 1,1'-ferrocenediyl scaffold was explored. This scaffold introduces the elements of linear flexibility and non-planar topology that are unconventional for this class of inhibitors. Data from 2-D NMR spectroscopic analyses of these complexes in solution support an anti (unstacked) arrangement of the pharmacophoric groups. Several complexes demonstrate single-digit picomolar in vitro activity in an HCV genotype-1b replicon system. One complex to arise from this investigation (10a) exhibits exceptional picomolar activity against HCV genotype 1a and 1b replicons, low hepatocellular cytotoxicity, and good pharmacokinetic properties in rat.

Design of Tumor Microenvironment-Responsive Drug-Drug Micelle for Cancer Radiochemotherapy.

Concomitant radiochemotherapy is a major therapeutic strategy for treating malignant tumors. However, the greatest challenge is how to improve the therapeutic effect of radiochemotherapy to achieve the proper synergetic chemo-/radiotherapy for the tumor. In this study, ferrocenium (antitumor effect) and nitroimidazole (hypoxic cell radiosensitization) conjugates were synthesized to form amphiphilic ferrocenium-hexane-nitroimidazole (Fe-NI), which can self-assemble in aqueous solution. The Fe-NI micelles successfully encapsulate the hydrophobic chemotherapy drug doxorubicin (DOX) and are modified with hyaluronic acid (HA) by electrostatic interactions to form HA-Fe-NIs-DOX micelles. HA-Fe-NIs-DOX micelles rapidly release DOX under tumor hypoxia and a high glutathione (GSH) environment and achieve a synergetic chemo-/radiotherapy for the tumor based on the properties of nitroimidazoles and ferrocenes. The biodistribution results obtained in vivo reveal an effective accumulation in the tumor. The HA-Fe-NIs-DOX micelles show a significant radiosensitizing effect on the tumors, and the combination of chemotherapy and radiotherapy is realized for the treatment of tumor in vitro and in vivo. These findings illustrate that HA-Fe-NIs micelles are a promising candidate, which enhances the antitumor effects as a DOX delivery system, owing to the synergistic mechanisms of antitumor agents and chemo-/radiotherapy.

[Preclinical application of MR and fluorescent dual-modality imaging combined with photothermal therapy in HER-2 positive breast cancer].

Objective: To construct superparamagnetic iron oxide nanoparticles (SPIONs) coated on trastuzumab and indocyanine green (ICG) and then investigate whether the coated nanoparticles (NPs) targeted to human epidermal growth factor receptor-2 (HER-2) receptors on breast cancer cells in vitro and in vivo. Methods: The Fe(3)O(4)-trastuzumab-ICG NPs were constructed. And a series of characteristics of the NPs were evaluated. The uptake ability of SK-BR-3, a HER-2 positive breast cancer cell, was observed by transmission electron microscopy. Then the NPs were injected in the tail veins of SK-BR-3 xenograft tumor-bearing mice to observe the aggregation of NPs in the tumor sites by MRI and fluorescent imaging. Furthermore, when the NPs was gathered at the tumor sites, the near infrared thermal imaging system was used to monitor the tumor temperature after the near infrared radiation. Results: The successfully constructed Fe(3)O(4)-trastuzumab-ICG NPs had the size of (25.93±4.25) nm. The absorption peak was 828 nm, which was as same as the emission wavelength of ICG. The NPs had a high relaxation rate of approximately 107.65 mM(-1)·s(-1). The maximum temperature of NPs solution could reach to 57.8℃ after continuous near infrared laser irradiation. The transmission electron microscopy imaging revealed that the NPs could target and enter into the endoplasmic reticulum of SK-BR-3 cells. MRI analysis showed the lowest T(2) relaxation time in the tumor sites 24 h after tail vein injection of the NPs. The △T(2) of the tumor sites in the Fe(3)O(4)-trastuzumab-ICG group (30.7±4.8) ms was higher compared with that of control group (3.1±1.1) ms, Fe(3)O(4)-IgG-ICG group (4.4±0.9) ms and trastuzumab + Fe(3)O(4)-trastuzumab-ICG group (11.3±3.8) ms., respectively, all showing statistically significant differences (P<0.05). The fluorescence imaging revealed that the NPs was concentrated transiently in the intraperitoneal organs and tumor sites, then excreted into the bladder. After 24 h, there was an obvious aggregation in the tumor sites. The near infrared thermal imaging experiments showed that the temperature of tumor sites in Fe(3)O(4)-trastuzumab-ICG group could go up to 49.4℃ after continuous near infrared light irradiation. Conclusion: The newly constructed Fe(3)O(4)-trastuzumab-ICG NPs have the potential to act as a multifunctional imaging agent and a powerful tool for photothermal therapy for HER-2 positive breast cancer.

Evaluation of iron transport from ferrous glycinate liposomes using Caco-2 cell model.

BACKGROUND: Iron fortification of foods is currently a strategy employed to fight iron deficiency in countries. Liposomes were assumed to be a potential carrier of iron supplements. OBJECTIVE: The objective of this study was to investigate the iron transport from ferrous glycinate liposomes, and to estimate the effects of liposomal carriers, phytic acid, zinc and particle size on iron transport using Caco-2 cell models. METHODS: Caco-2 cells were cultured and seeded in DMEM medium. Minimum essential medium was added to the basolateral side. Iron liposome suspensions were added to the apical side of the transwell. RESULTS: The iron transport from ferrous glycinate liposomes was significantly higher than that from ferrous glycinate. In the presence of phytic acid or zinc ion, iron transport from ferrous glycinate liposomes and ferrous glycinate was evidently inhibited, and iron transport decreased with increasing phytic acid concentration. Iron transport was decreased with increase of particle size increasing of ferrous glycinate liposome. CONCLUSION: Liposomes could behave as more than a simple carrier, and iron transport from liposomes could be implemented via a mechanism different from the regulated non-heme iron pathway.

In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in children.

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Iron bioavailability from fresh cheese fortified with iron-enriched yeast.

PURPOSE: An iron-enriched yeast able to lyse at body temperature was developed for iron fortification of chilled dairy products. The aim was to evaluate iron (Fe) absorption from iron-enriched yeast or ferrous sulfate added to fresh cheese. METHODS: Two stable isotope studies with a crossover design were conducted in 32 young women. Fe absorption from fresh cheese fortified with iron-enriched yeast (2.5 mg 58Fe) was compared to that from ferrous sulfate (2.5 mg 57Fe) when ingested with fresh cheese alone or with fresh cheese consumed with bread and butter. Iron absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean fractional iron absorption from fresh cheese fortified with iron-enriched yeast consumed alone was significantly lower than from the cheese fortified with FeSO4 (20.5 vs. 28.7 %; p = 0.0007). When the fresh cheese was consumed with bread and butter, iron absorption from both fortificants decreased to 6.9 % from the iron-enriched yeast compared to 8.4 % from ferrous sulfate. The relative bioavailability of the iron-enriched yeast compared to ferrous sulfate was 0.72 for the cheese consumed alone and 0.82 for cheese consumed with bread and butter (p = 0.157). CONCLUSIONS: Iron from iron-enriched yeast was 72-82 % as well absorbed as ferrous sulfate indicating that the yeast lysed during digestion and released its iron.

Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration.