Strategies for Oral Delivery of Metal-Saturated Lactoferrin

Author(s): Przemysław Gajda-Morszewski, Klaudyna Śpiewak-Wojtyła, Maria Oszajca, Małgorzata Brindell*

Journal Name: Current Protein & Peptide Science

Volume 20 , Issue 11 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Lactoferrin was isolated and purified for the first time over 50-years ago. Since then, extensive studies on the structure and function of this protein have been performed and the research is still being continued. In this mini-review we focus on presenting recent scientific efforts towards the elucidation of the role and therapeutic potential of lactoferrin saturated with iron(III) or manganese(III) ions. The difference in biological activity of metal-saturated lactoferrin vs. the unmetalated one is emphasized. The strategies for oral delivery of lactoferrin, are also reviewed, with particular attention to the metalated protein.

Keywords: Lactoferrin, iron saturated-lactoferrin, manganese-saturated lactoferrin, oral delivery, biological activity, metalated protein.

Magnuson, J.S.; Henry, J.F.; Yip, T.T.; Hutchens, T.W. Structural homology of human, bovine, and porcine milk lactoferrins: Evidence for shared antigenic determinants. Pediatr. Res., 1990, 28, 176-181.
Lönnerdal, B.; Jiang, R.; Du, X. Bovine lactoferrin can be taken up by the human intestinal lactoferrin receptor and exert bioactivities. J. Pediatr. Gastroenterol. Nutr., 2011, 53, 606-614.
Anderson, B.F.; Baker, H.M.; Norris, G.E.; Rumball, S.V.; Baker, E.N. Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins. Nature, 1990, 344, 784-787.
Luis Moreno-Expósitoa, L.; Illescas-Montesb, R.; Melguizo-Rodrígueza, L.; Ruiza, C.; Ramos-Torrecillasa, J.; de Luna-Bertosa, E. Multifunctional capacity and therapeutic potential of lactoferrin. Life Sci., 2018, 196, 61-64.
Brock, J.H. Lactoferrin – 50 years on. Biochem. Cell Biol., 2012, 90, 245-251.
Drago-Serrano, M.E.; Campos-Rodríguez, R.; César Carrero, J.; de la Garza, M. Lactoferrin: Balancing ups and downs of inflammation due to microbial infections. Int. J. Mol. Sci., 2017, 18, 501.
Rosa, L.; Cutone, A.; Lepanto, M.S.; Paesano, R.; Valenti, P. Lactoferrin: A natural glycoprotein involved in iron and inflammatory homeostasis. Int. J. Mol. Sci., 2017, 18, 1985.
Aisen, P.; Leibman, A. Lactoferrin and transferrin: A comparative study. Biochim. Biophys. Acta Protein Struct., 1972, 257, 314-323.
Anderson, B.F.; Baker, H.M.; Norris, G.E.; Rice, D.W.; Baker, E.N. Structure of human lactoferrin: Crystallographic structure analysis and refinement at 2.8 A resolution. J. Mol. Biol., 1989, 209, 711-734.
Troost, F.J.; Steijns, J.; Saris, W.H.M.; Brummer, R.J.M. Gastric digestion of bovine lactoferrin in vivo in adults. J. Nutr., 2001, 131, 2101-2104.
Baker, H.M.; Baker, E.N. A structural perspective on lactoferrin function. Biochem. Cell Biol., 2012, 90, 320-328.
Chilton, C.H.; Crowther, G.S.; Śpiewak, K.; Brindell, M.; Singh, G.; Wilcox, M.H.; Monaghan, T.M. Potential of lactoferrin to prevent antibiotic-induced Clostridium difficile infection. J. Antimicrob. Chemother., 2016, 71(4), 975-985.
Kanwar, J.R.; Mahidhara, G.; Kanwar, R.K. Novel alginate-enclosed chitosan-calcium phosphate-loaded iron-saturated bovine lactoferrin nanocarriers for oral delivery in colon cancer therapy. Nanomedicine (Lond.), 2012, 7, 1521-1550.
Kanwar, J.R.; Palmano, P.K.; Sun, X.; Kanwar, R.K.; Gupta, R.; Haggarty, N. “Iron saturated” lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy. Immunol. Cell Biol., 2008, 86, 277-288.
Kanwar, R.K.; Kanwar, J.R. Immunomodulatory lactoferrin in the regulation of apoptosis modulatory proteins in cancer. Protein Pept. Lett., 2013, 20, 450-458.
Samarasinghe, R.M.; Kanwar, R.K.; Kanwar, J.R. The effect of oral administration of iron saturated-bovine lactoferrin encapsulated chitosan-nanocarriers on osteoarthritis. Biomaterials, 2014, 35, 7522-7534.
Ainscough, E.W.; Brodie, A.M.; Plowman, J.E. The chromium, manganese, cobalt, and copper complexes of human lactoferrin. Inorg. Chim. Acta, 1979, 33, 149-153.
Lew, L.C.; Liong, M.T.; Gan, C.Y. Growth optimization of Lactobacillus rhamnosus FTDC 8313 and the production of putative dermal bioactives in the presence of manganese and magnesium ions. J. Appl. Microbiol., 2013, 114(2), 526-535.
Lönnerdal, B.; Keen, C.L.; Hurley, L.S. Manganese binding proteins in human and cow’s milk. Am. J. Clin. Nutr., 1985, 41, 550-559.
Marchetti, M.; Superti, F.; Ammendolia, M.G.; Rossi, P.; Valenti, P.; Seganti, L. Inhibition of poliovirus type 1 infection by iron-, manganese and zinc saturated lactoferrin. Med. Microbiol. Immunol., 1999, 187(4), 199-204.
Superti, F.; Siciliano, R.; Rega, B.; Giansanti, F.; Valenti, P.; Antonini, G. Involvement of bovine lactoferrin metal saturation, sialic acid and protein fragments in the inhibition of rotavirus infection. Biochim. Biophys. Acta, 2001, 1528(2-3), 107-115.
Pietrantoni, A.; Ammendolia, M.G.; Superti, F. Bovine lactoferrin: Involvement of metal saturation and carbohydrates in the inhibition of influenza virus infection. Biochem. Cell Biol., 2012, 90(3), 442-448.
Śpiewak, K.; Majka, G.; Pilarczyk-Żurek, M.; Nowak, P.M.; Woźniakiewicz, M.; Pietrzyk, P.; Korzeniak, T.; Stochel-Gaudyn, A.; Fyderek, K.; Strus, M.; Brindell, M. Mn3+-saturated bovine lactoferrin as a new complex with potential prebiotic activities for dysbiosis treatment and prevention – On the synthesis, chemical characterization and origin of biological activity. J. Funct. Foods, 2017, 38, 264-272.
Majka, G.; Więcek, G.; Śróttek, M.; Śpiewak, K.; Brindell, M.; Koziel, J.; Marcinkiewicz, J.; Strus, M. The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation. BioMetals, 2016, 29(6), 1019-1033.
Takeuchi, T.; Jyonotsuka, T.; Kamemori, N.; Kawano, G.; Shimizu, H.; Ando, K.; Harada, E. Enteric-formulated lactoferrin was more effectively transported into blood circulation from gastrointestinal tract in adult rats. Exp. Physiol., 2006, 91, 1033-1040.
Hejazi, R.; Amiji, M. Chitosan-based gastrointestinal delivery systems. J. Control. Release, 2003, 89, 151-165.
Onishi, H.; Machida, Y.; Koyama, K. Preparation and in vitro characteristics of lactoferrin loaded chitosan microparticles. Drug Dev. Ind. Pharm., 2007, 33, 641-647.
Onishi, H.; Koyama, K.; Sakata, O.; Machida, Y. Preparation and in vitro evaluation of chitosan-coated alginate/calcium complex microparticles loaded with fluorescein-labeled lactoferrin. Yakugaku Zasshi, 2009, 129, 1507-1514.
Kilic, E.; Novoselova, M.V.; Hui Lim, S.; Pyataev, N.A.; Pinyaev, S.I.; Kulikov, O.A.; Sindeeva, O.A.; Mayorova, O.A.; Murney, R.; Antipina, M.N.; Haigh, B.; Sukhorukov, G.B.; Kiryukhin, M.V. Formulation for oral delivery of lactoferrin based on bovine serum albumin and tannic acid multilayer microcapsules. Sci. Rep., 2017, 7, 44159.
Yao, X.; Bunt, C.; Cornish, J.; Quek, S.Y.; Wen, J. Oral delivery of lactoferrin: A review. Int. J. Pept. Res. Ther., 2013, 19, 125-134.
Onishi, H. Lactoferrin delivery systems: Approaches for its more effective use. Expert Opin. Drug Deliv., 2011, 8, 1469-1479.
Monaghan, T.; Braim, S.; Spiewak, K.; Brindell, M.; Alexander, C. Novel lactoferrin-loaded alginate microbeads sisplay anti-Clostridium difficile defence properties. Gut, 2018, 61(Suppl. 1), A194-A195.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 23 October, 2019
Page: [1046 - 1051]
Pages: 6
DOI: 10.2174/1389203720666190513085839
Price: $65

Article Metrics

PDF: 28
PRC: 1