International Journal of Biomedical Engineering and Clinical Science

Research Article | | Peer-Reviewed |

Safety Evaluation of Recombinant Bovine Lactoferrin as a Novel Biomaterial

Received: 1 February 2024    Accepted: 20 February 2024    Published: 7 March 2024
Views:       Downloads:

Share This Article

Abstract

This study introduces the physical principles and safety evaluation of recombinant bovine lactoferrin (fusion factor) as an innovative biomaterial. Fusion factor is a recombinant lactoferrin expressed by fusing lactoferrin, which has natural biological defense function, with other peptide segments through sequence optimization. It is named fusion factor. Its molecular weight is about 36kDa, which is much greater than the 1kDa molecular weight limit of macromolecular transdermal absorption, so it is not absorbed when used externally on the epithelial mucosa. The lactoferrin based biological defense functional peptide segment in the fusion factor can neutralize the virus by binding to viral protein nucleic acid through the physical action of charge adsorption, and can also compete with cell receptors to inhibit virus infection in cells. The molar ratio of the transmembrane peptide (Pep-1) fragment to the carrier protein is 1:1, so only the transport protein is anchored to the cell surface, forming a physical isolation protein protective wall against viruses and bacteria, without penetrating the cell or damaging the cell membrane. The fusion factor and its derived vaginal bacteria blocking gel have no significant toxicity, sensitization, anaphylaxis or delayed hypersensitivity in vitro cell experiments, in vivo animal experiments and clinical observation tests, and have no side effects with highly safety.

DOI 10.11648/j.ijbecs.20241001.11
Published in International Journal of Biomedical Engineering and Clinical Science (Volume 10, Issue 1, March 2024)
Page(s) 1-8
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Recombinant Bovine Lactoferrin, Fusion Factor, Biological Defense, Physical Effects, Security

References
[1] Chen Y, Ge YQ, Zhang LM, et al. Research progress and application prospects of mammalian defense peptides. Progress in Biochemistry and Biophysics, 2001 https://doi.org/10.3321/j.issn: 1000-3282.2001.01.004
[2] Drayton M, Deisinger JP, Ludwig KC, Raheem N, Müller A, Schneider T, Straus SK. Host Defense Peptides: Dual Antimicrobial and Immunomodulatory Action. Int J Mol Sci. 2021 Oct 16; 22(20): 11172. https://doi.org/10.3390/ijms222011172
[3] Roca-Pinilla R, Lisowski L, Arís A, Garcia-Fruitós E. The future of recombinant host defense peptides. Microb Cell Fact. 2022 Dec 21; 21(1): 267. https://doi.org/10.1186/s12934-022-01991-2
[4] Ma XM, Su JX, Chen Y, et al. Research progress on the structure and function of four main proteins in animal milk and their separation and purification methods. Journal of Northwest University for Nationalities (Natural Science Edition), 2022, 43(02): 74-79. https://doi.org/10.14084/j.cnki.cn62-1188/n.2022.02.009
[5] Berlutti F, Pantanella F, Natalizi T, Frioni A, Paesano R, Polimeni A, Valenti P. Antiviral properties of lactoferrin--a natural immunity molecule. Molecules. 2011 Aµg 16; 16(8): 6992-7018. https://doi.org/10.3390/molecules16086992
[6] Xiao HY, Lan XY, Zhang PH. Research progress on the biological functions of lactoferrin. China Dairy Cattle. 2021(04): 46-50. https://doi.org/10.19305/j.cnki.11-3009/s.2021.04.011
[7] Brock JH. Lactoferrin--50 years on. Biochem Cell Biol. 2012 Jun; 90(3): 245-51. https://doi.org/10.1139/o2012-018
[8] Habault J, Poyet JL. Recent Advances in Cell Penetrating Peptide-Based Anticancer Therapies. Molecules. 2019 Mar 7; 24(5): 927. https://doi.org/10.3390/molecules24050927
[9] Morris MC, Depollier J, Mery J, Heitz F, Divita G. Nat Biotechnol. A peptide carrier for the delivery of biologically active proteins into mammalian cells. 2001 Dec; 19(12): 1173-6. https://doi.org/10.1038/nbt1201-1173
[10] Hu JW, Chen JJ, Tu W, et al. Toxicological safety study of lactoferrin bovine colostrum granules. Anhui Agricultural Science. 2012, 40(12): 7195-7198. https://doi.org/10.13989/j.cnki.0517-6611.2012.12.041
[11] Dai YN, Yang XZ, Wang JW, et al. Safety evaluation of recombinant human lactoferrin as a new raw material for cosmetics. Chinese Journal of Health Laboratory Technology, 2017, 27(13): 1851-1854+1862.
[12] Biernbaum EN, Gnezda A, Akbar S, Franklin R, Venturelli PA, McKillip JL. Lactoferrin as an antimicrobial against Salmonella enterica and Escherichia coli O157:H7 in raw milk. JDS Commun. 2021 Mar 12; 2(3): 92-97. https://doi.org/10.3168/jdsc.2020-0030
[13] Ding B, Chen Z. Molecular interactions between cell penetrating peptide Pep-1 and model cell membranes. J Phys Chem B. 2012 Mar 1; 116(8): 2545-52. https://doi.org/10.1021/jp209604m
[14] Baker EN, Baker HM. Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci. 2005 Nov; 62(22): 2531-9. https://doi.org/10.1007/s00018-005-5368-9
[15] Ekins A, Khan AG, Shouldice SR, Schryvers AB. Lactoferrin receptors in gram-negative bacteria: insights into the iron acquisition process. Biometals. 2004 Jun; 17(3): 235-43. https://doi.org/10.1023/b:biom.0000027698.43322.60
[16] Drobni, P.; Naslund, J.; Evander, M. Lactoferrin inhibits human papilloma virus binding and uptake in vitro. Antiviral Res. 2004, 64, 63-68. https://pubmed.ncbi.nlm.nih.gov/15451180/
[17] Mistry N, Drobni P, Näslund J, Sunkari VG, Jenssen H, Evander M. The anti-papillomavirus activity of human and bovine lactoferricin. Antiviral Res. 2007 Sep; 75(3): 258-65. https://doi.org/10.1016/j.antiviral.2007.03.012
[18] Zhang P, Moreno R, Lambert PF, DiMaio D. Cell-penetrating peptide inhibits retromer-mediated human papillomavirus trafficking during virus entry. Proc Natl Acad Sci U S A. 2020 Mar 17; 117(11): 6121-6128. https://doi.org/10.1073/pnas.1917748117
[19] Shahbazi S, Bolhassani A. Comparison of six cell penetrating peptides with different properties for in vitro and in vivo delivery of HPV16 E7 antigen in therapeutic vaccines. Int Immunopharmacol. 2018 Sep; 62: 170-180. https://doi.org/10.1016/j.intimp.2018.07.006
[20] Zhang P, Monteiro da Silva G, Deatherage C, Burd C, DiMaio D. Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking. Cell. 2018 Sep 6; 174(6): 1465-1476.e13. https://doi.org/10.1016/j.cell.2018.07.031
[21] Granadillo M, Vallespi MG, Batte A, Mendoza O, Soria Y, Lµgo VM, Torrens I. A novel fusion protein-based vaccine comprising a cell penetrating and immunostimulatory peptide linked to human papillomavirus (HPV) type 16 E7 antigen generates potent immunologic and anti-tumor responses in mice. Vaccine. 2011 Jan 29; 29(5): 920-30. https://doi.org/10.1016/j.vaccine.2010.11.083
Cite This Article
  • APA Style

    Sun, J., Zhang, S., Wang, Y., Wei, J., Teng, Y., et al. (2024). Safety Evaluation of Recombinant Bovine Lactoferrin as a Novel Biomaterial. International Journal of Biomedical Engineering and Clinical Science, 10(1), 1-8. https://doi.org/10.11648/j.ijbecs.20241001.11

    Copy | Download

    ACS Style

    Sun, J.; Zhang, S.; Wang, Y.; Wei, J.; Teng, Y., et al. Safety Evaluation of Recombinant Bovine Lactoferrin as a Novel Biomaterial. Int. J. Biomed. Eng. Clin. Sci. 2024, 10(1), 1-8. doi: 10.11648/j.ijbecs.20241001.11

    Copy | Download

    AMA Style

    Sun J, Zhang S, Wang Y, Wei J, Teng Y, et al. Safety Evaluation of Recombinant Bovine Lactoferrin as a Novel Biomaterial. Int J Biomed Eng Clin Sci. 2024;10(1):1-8. doi: 10.11648/j.ijbecs.20241001.11

    Copy | Download

  • @article{10.11648/j.ijbecs.20241001.11,
      author = {Jiamiao Sun and Sumin Zhang and Yong Wang and Jinchi Wei and Yonghui Teng and Binghua Quan and Xiaoming Pang and Honghong Deng and Chiming Wei},
      title = {Safety Evaluation of Recombinant Bovine Lactoferrin as a Novel Biomaterial},
      journal = {International Journal of Biomedical Engineering and Clinical Science},
      volume = {10},
      number = {1},
      pages = {1-8},
      doi = {10.11648/j.ijbecs.20241001.11},
      url = {https://doi.org/10.11648/j.ijbecs.20241001.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijbecs.20241001.11},
      abstract = {This study introduces the physical principles and safety evaluation of recombinant bovine lactoferrin (fusion factor) as an innovative biomaterial. Fusion factor is a recombinant lactoferrin expressed by fusing lactoferrin, which has natural biological defense function, with other peptide segments through sequence optimization. It is named fusion factor. Its molecular weight is about 36kDa, which is much greater than the 1kDa molecular weight limit of macromolecular transdermal absorption, so it is not absorbed when used externally on the epithelial mucosa. The lactoferrin based biological defense functional peptide segment in the fusion factor can neutralize the virus by binding to viral protein nucleic acid through the physical action of charge adsorption, and can also compete with cell receptors to inhibit virus infection in cells. The molar ratio of the transmembrane peptide (Pep-1) fragment to the carrier protein is 1:1, so only the transport protein is anchored to the cell surface, forming a physical isolation protein protective wall against viruses and bacteria, without penetrating the cell or damaging the cell membrane. The fusion factor and its derived vaginal bacteria blocking gel have no significant toxicity, sensitization, anaphylaxis or delayed hypersensitivity in vitro cell experiments, in vivo animal experiments and clinical observation tests, and have no side effects with highly safety.
    },
     year = {2024}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - Safety Evaluation of Recombinant Bovine Lactoferrin as a Novel Biomaterial
    AU  - Jiamiao Sun
    AU  - Sumin Zhang
    AU  - Yong Wang
    AU  - Jinchi Wei
    AU  - Yonghui Teng
    AU  - Binghua Quan
    AU  - Xiaoming Pang
    AU  - Honghong Deng
    AU  - Chiming Wei
    Y1  - 2024/03/07
    PY  - 2024
    N1  - https://doi.org/10.11648/j.ijbecs.20241001.11
    DO  - 10.11648/j.ijbecs.20241001.11
    T2  - International Journal of Biomedical Engineering and Clinical Science
    JF  - International Journal of Biomedical Engineering and Clinical Science
    JO  - International Journal of Biomedical Engineering and Clinical Science
    SP  - 1
    EP  - 8
    PB  - Science Publishing Group
    SN  - 2472-1301
    UR  - https://doi.org/10.11648/j.ijbecs.20241001.11
    AB  - This study introduces the physical principles and safety evaluation of recombinant bovine lactoferrin (fusion factor) as an innovative biomaterial. Fusion factor is a recombinant lactoferrin expressed by fusing lactoferrin, which has natural biological defense function, with other peptide segments through sequence optimization. It is named fusion factor. Its molecular weight is about 36kDa, which is much greater than the 1kDa molecular weight limit of macromolecular transdermal absorption, so it is not absorbed when used externally on the epithelial mucosa. The lactoferrin based biological defense functional peptide segment in the fusion factor can neutralize the virus by binding to viral protein nucleic acid through the physical action of charge adsorption, and can also compete with cell receptors to inhibit virus infection in cells. The molar ratio of the transmembrane peptide (Pep-1) fragment to the carrier protein is 1:1, so only the transport protein is anchored to the cell surface, forming a physical isolation protein protective wall against viruses and bacteria, without penetrating the cell or damaging the cell membrane. The fusion factor and its derived vaginal bacteria blocking gel have no significant toxicity, sensitization, anaphylaxis or delayed hypersensitivity in vitro cell experiments, in vivo animal experiments and clinical observation tests, and have no side effects with highly safety.
    
    VL  - 10
    IS  - 1
    ER  - 

    Copy | Download

Author Information
  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, USA

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China

  • Department of Infectious Diseases, Chinese Academy of Biomedical Sciences, Hong Kong, China; Department of Nano Medicine, American Nanomedicine Institute, Baltimore, USA

  • Sections