Skip to main content

Advertisement

SpringerLink
Log in

Potential of Alginate Encapsulated Ferric Saccharate Microemulsions to Ameliorate Iron Deficiency in Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

A Correction to this article was published on 17 December 2022

This article has been updated

Abstract

Iron deficiency is one of the most prominent mineral deficiencies around the world, which especially affects large population of women and children. Development of new technologies to combat iron deficiency is on high demand. Therefore, we developed alginate microcapsule with encapsulated iron that had better oral iron bioavailability. Microcapsules containing iron with varying ratios of sodium alginate ferric(III)-saccharide were prepared using emulsification method. In vitro studies with Caco-2 cells suggested that newly synthesized microemulsions had better iron bioavailability as compared to commercially available iron dextran formulations. Ferrozine in vitro assay showed that alginate-encapsulated ferric galactose microemulsion (AFGM) had highest iron bioavailability in comparison to other four ferric saccharate microemulsions, namely AFGlM, AFMM, AFSM, and AFFM synthesized in our laboratory. Mice studies also suggested that AFGM showed higher iron absorption as indicated by increased serum iron, hemoglobin, and other hematopoietic measures with almost no toxicity at tested doses. Development of iron-loaded microemulsions leads to higher bioavailability of iron and can provide alternative strategies to treat iron deficiency.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Change history

Abbreviations

FGlC:

Ferric-glucose complex

FSC:

Ferric-sorbitol complex

FFC:

Ferric-fructose complex

FMC:

Ferric-mannose complex

FGC:

Ferric-galactose complex

AFGM:

Alginate-encapsulated ferric galactose microemulsion

AFGlM:

Alginate-encapsulated ferric glucose microemulsion

AFMM:

Alginate-encapsulated ferric mannose microemulsion

AFSM:

Alginate-encapsulated ferric sorbitol microemulsion

AFFM:

Alginate-encapsulated ferric fructose microemulsion

References

  1. Kaur M, Bassi R, Sharma S (2011) Impact of nutrition education in reducing iron deficiency anemia in adolescent girls. Ind J Fund Appl Life Sci 1:222–228

    Google Scholar 

  2. Rohner F, Ernst FO, Arnold M, Hilbe M, Biebinger R, Ehrensperger F, Langhans W, Hurrell RF, Zimmermann MB (2007) Synthesis, characterization, and bioavailability in rats of ferric phosphate nanoparticles. J Nutr 137:614–619

    CAS  PubMed  Google Scholar 

  3. Brock C, Curry H, Hanna C (1985) Adverse effects of iron supplementation: a comparative trial of a wax-matrix iron preparation and conventional ferrous sulfate tablets. Clin Ther 7:568–573

    CAS  PubMed  Google Scholar 

  4. Litovitz TL, Klein-Schwartz W, Jr Rodgers GC, Cobaugh DJ, Youniss J, Omslaer JC, May ME, Woolf AD, Benson BE (2002) 2001 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 20:391–452

    Article  PubMed  Google Scholar 

  5. Geisser P, Baer M, Schaub E (1992) Structure/histotoxicity relationship of parenteral iron preparations. Arzneim Forsch 42:1439–1452

    CAS  Google Scholar 

  6. Sharma N (2001) Iron absorption: IPC therapy is superior to conventional iron salts. Obstet Gynecol, pp 515–519

  7. McCord JM (1998) Iron, free radicals, and oxidative injury. Semin Hematol 35:5–12

    CAS  PubMed  Google Scholar 

  8. Geisser P (1990) In vitro studies on interactions of iron salts and complexes with food stuffs and medicaments. Arzneimittelforschung 40:754–760

    CAS  PubMed  Google Scholar 

  9. Jacobs P, Johnson G, Wood L (1984) Oral iron therapy in human subjects, comparative absorption between ferrous salts and iron polymaltose. J Med 15:367–377

    CAS  PubMed  Google Scholar 

  10. Saha L, Pandhi P, Gopalan S, Malhotra S, Saha PK (2007) Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anemia in pregnant women. Med Gen Med 9:1–15

    Article  Google Scholar 

  11. Schümann K, Ettle T, Szegner B, Elsenhans B, Solomons NW (2007) On risks and benefits of iron supplementation recommendations for iron intake revisited. J Trace Elem Med Biol 21:147–168

    Article  PubMed  Google Scholar 

  12. Zimmermann MB (2004) The potential of encapsulated iron compounds in food fortification: a review. Int J Vitam Nutr Res 74:453–61

    Article  CAS  PubMed  Google Scholar 

  13. Wegmüller R, Zimmermann MB, Moretti D, Arnold M, Langhans W, Hurrell RF (2004) Particle size reduction and encapsulation affect the bioavailability of ferric pyrophosphate in rats. J Nutr 134:3301–3304

    PubMed  Google Scholar 

  14. Yeo Y, Baek N, Park K (2001) Microencapsulation methods for delivery of protein drugs. Biotechnol Bioprocess Eng 6:213–230

    Article  CAS  Google Scholar 

  15. Bock N, Dargaville TR, Woodruff MA (2014) Controlling microencapsulation and release of micronized proteins using poly (ethylene glycol) and electrospraying. Eur J Pharm Biopharm 87:366–377

    Article  CAS  PubMed  Google Scholar 

  16. Walter E, Moelling K, Pavlovic J, Merkle HP (1999) Microencapsulation of DNA using poly(DL-lactide-co-glycolide): stability issues and release characteristics. J Control Release 20:361–74

    Article  Google Scholar 

  17. Alexakis T, Boadi DK, Quong D, Groboillot A, O’Neill I, Poncelet D, Neufeld RJ (1995) Microencapsulation of DNA within alginate microspheres and crosslinked chitosan membranes for in vivo application. Appl Biochem Biotechnol 50(1):93–106

    Article  CAS  PubMed  Google Scholar 

  18. Estevinho BN, Damas AM, Martins P, Rocha F (2014) Microencapsulation of β-galactosidase with different biopolymers by a spray-drying process. Food Res Int 64:134–140

    Article  CAS  Google Scholar 

  19. Davila-Hicks P, Theil EC, Lönnerdal B (2004) Iron in ferritin or in salts (ferrous sulfate) is equally bioavailable in nonanemic women. Am J Clin Nutr 80:936–40

    CAS  PubMed  Google Scholar 

  20. Theil EC, Chen H, Miranda C, Janser H, Elsenhans B, Núñez MT, Pizarro F, Schümann K (2012) Absorption of iron from ferritin is independent of heme iron and ferrous salts in women and rat intestinal segments. J Nutr 142:478–483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Silverstein SB, Rodgers GM (2004) Parenteral iron therapy options. Am J Hematol 76:74–78

    Article  CAS  PubMed  Google Scholar 

  22. Ortiz R, Tob-lli JE, Romero JD, Monterrosa B, Frer C, Macagno E, Breymann C (2011) Efficacy and safety of oral iron(III) polymaltose complex versus ferrous sulfate in pregnant women with iron-deficiency anemia: a multicenter, randomized, controlled study. J Matern Fetal Neonatal Med 24:1347–52

    Article  PubMed  Google Scholar 

  23. Yasa B, Agaoglu L, Unuvar E (2011) Efficacy, tolerability, and acceptability of iron hydroxide polymaltose complex versus ferrous sulfate: a randomized trial in pediatric patients with iron deficiency anemia. Int J Pediatr 2011:1-6

  24. Silverberg DS, Blum M, Peer G, Kaplan E, Iaina A (1996) Intravenous ferric saccharate as an iron supplement in dialysis patients. Nephron 72:413–7

    Article  CAS  PubMed  Google Scholar 

  25. Richard D, Ibrahim M, Yvonne F, Laura C, Deepti HN (2012) Comparative efficacy of three forms of parenteral iron. J Blood Transfus 2012:1–3

    Google Scholar 

  26. Markus RJ, Thomas N, Sören F, Uwe W, Ute K, Peter L (2012) Iron Oxide/Hydroxide nanoparticles with negatively charged shells show increased uptake in Caco-2 cells. Mol Pharmaceutics 9:1628–1637

    Article  Google Scholar 

  27. Rokstad AM, Brekke O, Steinkjer B, Ryan L, Kolláriková G, Strand BL, Skjåk-Bræk G, Lacík I, Espevik E, Mollnes TE (2011) Alginate microbeads are complement compatible, in contrast to polycation containing microcapsules, as revealed in a human whole blood model. Acta Biomater 7:2566–2578

    Article  CAS  PubMed  Google Scholar 

  28. Sk T, Bilodeau S, Dusseault J, Langlois G, Hallé JP, Yahia LH (2011) Biocompatibility and physicochemical characteristics of alginate–polycation microcapsules. Acta Biomater 7:1683–1692

    Article  Google Scholar 

  29. Geetha K, Raghavan MSS, Kulshreshtha SK, Sasikala R, Rao CP (1995) Transition- metal saccharide chemistry: synthesis, spectroscopy, electrochemistry and magnetic susceptibility studies of iron (III) complexes of mono- and disaccharides. Carbohydr Res 271:163–175

    Article  CAS  Google Scholar 

  30. Khosroyar S, Akbarzade A, Arjoman M, Safekordi AA, Mortazavi SA (2012) Ferric – Saccharate capsulation with alginate coating using the emulsification method. Afr J Microbiol Res 6:2455–2461

    CAS  Google Scholar 

  31. Fish W (1988) Rapid colorimetric micro method for the quantitation of complexed iron in biological samples. Methods Enzymol 158:357–364

    Article  CAS  PubMed  Google Scholar 

  32. Shappell NWE (2003) Rgovaline toxicity on Caco-2 cells as assessed by MTT, alamar Blue, and DNA assays. In Vitro Cell Dev Biol Anim 39:329–35

    Article  CAS  PubMed  Google Scholar 

  33. Reeves PG, Nielsen FH, Fahey GC (1993) AIN-93 purified the diets for laboratory rodents. J Nutr 123:1939–51

    CAS  PubMed  Google Scholar 

  34. Siek G, Lawlor J, Pelczar D, Sane M, Musto J (2002) Direct serum total iron-binding capacity assay suitable for automated analyzers. Clinic Chem 48:161–166

    Google Scholar 

  35. Sharma D, Mathur R, Singh P (1993) Iron metabolism: a review. Indian J Clin Biochem 8:80–101

    Google Scholar 

  36. Wills ED (1996) Mechanisms of lipid peroxide formation in animal tissues. Biochem J 99:667–676

    Article  Google Scholar 

  37. Wang H, Joseph JA (1999) Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med 27:612–616

    Article  CAS  PubMed  Google Scholar 

  38. Luck H (1963) Catalase. In: Bergemeyer HU (ed) Methods of enzymatic analysis. Acedemic Press, London, pp 885–891

    Google Scholar 

  39. Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophy 186:189–195

    Article  CAS  Google Scholar 

  40. Kiernan JA (2008) Histological and histochemical methods, 4th edn. Scion publishing Ltd, Oxfordshire

    Google Scholar 

  41. Corrons JLV, Miguel MA, Pujades MA, Migual-Sosa A, Cambiazzo S, Linares M, Dibarrart MT, Calvo MA (1995) Increased susceptibility of microcytic red blood cells to in vitro oxidative stress. Eur J Haematol 55:327–331

    Article  Google Scholar 

  42. Hawkins R (2007) Total iron binding capacity or transferrin concentration alone outperforms iron and saturation indices in predicting iron deficiency. Clinica Chemica Acta 380:203–207

    Article  CAS  Google Scholar 

  43. Okada S (1996) Iron-induced tissue damage and cancer: the role of reactive oxygen species-free radicals. Pathol Int 46:311–332

    Article  CAS  PubMed  Google Scholar 

  44. Golovin AA, Konvai VD (1991) Lipid peroxidation in patients with iron deficiency anemia complicated by frequent acute respiratory distress. Klin Med 69:73–75

    CAS  Google Scholar 

  45. Acharya J, Punchard NA, Taylor JA (1991) Red cell lipid peroxidation and antioxidant enzymes in iron deficiency. Eur J Haematol 4:287–291

    Google Scholar 

  46. Komerova A, Lece A, Skesters A, Silova A, Petuhovs V (1998) Anemia and antioxidant defence of the red blood cells. Mater Med Pol 30:12–15

    Google Scholar 

  47. Meral A, Tuncel P, Sürmen-Gür E, Ozbek R, Oztürk E, Günay U (2000) Lipid peroxidation and antioxidant status in beta-thalassemia. Pediatr Hemat Oncol 17:687–693

    Article  CAS  Google Scholar 

  48. Tekin S, Yavuzer M, Akar N, Cin S (2001) Possible effects of antioxidants status on increased platelet aggregation in childhood iron-deficiency anemia. Pediatr Int 43:74–77

    Article  CAS  PubMed  Google Scholar 

  49. Annan NT, Borza AD, Hansen LT (2008) Encapsulation in alginate-coated gelatin microspheres improves survival of the probiotic Bifidobacterium adolescentis 15703T during exposure to simulated gastro-intestinal conditions. Food Res Int 41:184–193

    Article  CAS  Google Scholar 

  50. Rodvien R, Tarassoli M, Crosby WH (1994) The structure of spleen in experimentally induced iron deficiency anemia. Am J Pathol 75:242–254

    Google Scholar 

  51. Sherman AR, Guthrie HA, Wolinsky I, Zulak IM (1972) Iron deficiency hyperlipidemia in 18-day-old rat pups: effects of milk lipids, lipoprotein lipase and triglycarride synthesis. J Nutr 8:152–162

    Google Scholar 

Download references

Acknowledgments

We acknowledge Dr. Vikas Rishi (NABI, Mohali) for his suggestions and help with analysis.

Funding Sources

Research was supported by the Department of Biotechnology and National Agri-Food Biotechnology Institute grants.

Author information

Authors and Affiliations

  1. National Agri Food Biotechnology Institute, Mohali, Punjab, India

    Stanzin Angmo, Kamalendra Yadav, Hariom Yadav & Nitin Kumar Singhal

  2. Department of Biochemistry, Panjab University, Chandigarh, Punjab, India

    Kimmi Mukhija, Kirti Singhal & Rajat Sandhir

  3. Present Address: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Hariom Yadav

Authors
  1. Kimmi Mukhija
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kirti Singhal
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stanzin Angmo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kamalendra Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hariom Yadav
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rajat Sandhir
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nitin Kumar Singhal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nitin Kumar Singhal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mukhija, K., Singhal, K., Angmo, S. et al. Potential of Alginate Encapsulated Ferric Saccharate Microemulsions to Ameliorate Iron Deficiency in Mice. Biol Trace Elem Res 172, 179–192 (2016). https://doi.org/10.1007/s12011-015-0564-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-015-0564-4

Keywords

Search

Navigation