Lactoferrin in Biomedical Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (10 May 2023) | Viewed by 36200

Special Issue Editors


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Guest Editor
Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185 Rome, Italy
Interests: human microbiota and diseases; intracellular facultative bacteria; antiviral/antibacterial action of lactoferrin

E-Mail Website
Guest Editor
Department of Public Health Sciences, Sapienza University of Rome, Piazzale A. Moro 5, 00185 Rome, Italy
Interests: lactoferrin; lactoferrin structure and funtions; in vitro and in vivo bacterial infections; in vitro and in vivo viral infections; inflammation; iron and inflammatory homeostasis disorders
Department of Public Health and Infectious Diseases, University of Rome “La Sapienza”, 00185 Rome, Italy
Interests: lactoferrin; lactoferrin structure and functions, in vitro and in vivo bacterial infections; in vitro and in vivo viral infections; inflammation; iron and inflammatory homeostasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Lactoferrin (Lf), an iron-binding multifunctional cationic glycoprotein secreted by exocrine glands and neutrophils, is a bridge between natural and adaptative immunity. Bovine Lf (bLf) has been commercialized as nutraceutical product, having been declared as a compound “Generally Recognized as Safe” by the FDA and as a dietary supplement by EFSA.

This Special Issue aims to highlight some of the most significant contributions to the biomedical applications of Lf derived from different species, including bLf, which has been applied both in vitro and in vivo.

The topics of interest include (but are not limited to) Lf applications against microbial infections, iron and inflammatory homeostasis disorders, as well as immunomodulatory, antioxidant, and anticancer activities, with particular focus on the physicochemical characterization of Lf. The Lf receptors and the relationship between Lf and microbiota are pivotal for mechanisms of action. The development of new technologies that aim to improve its bioavailability should be considered. Original papers and review articles on Lf functions are welcome.

Dr. Maria Pia Conte
Prof. Dr. Piera Valenti
Dr. Luigi Rosa
Guest Editors

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Keywords

  • lactoferrin
  • lactoferrin physicochemical characterization
  • lactoferrin receptors
  • lactoferrin and microbiota
  • bacterial activity
  • viral activity
  • iron homeostasis
  • inflammation
  • immunomodulation
  • cancer
  • lactoferrin bioavailability

Published Papers (14 papers)

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Research

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34 pages, 8788 KiB  
Article
Antibacterial, Anti-Biofilm and Pro-Migratory Effects of Double Layered Hydrogels Packaged with Lactoferrin-DsiRNA-Silver Nanoparticles for Chronic Wound Therapy
by Mohammad Aqil M. Fathil and Haliza Katas
Pharmaceutics 2023, 15(3), 991; https://doi.org/10.3390/pharmaceutics15030991 - 19 Mar 2023
Cited by 8 | Viewed by 2262
Abstract
Antimicrobial resistance and biofilm formation in diabetic foot infections worsened during the COVID-19 pandemic, resulting in more severe infections and increased amputations. Therefore, this study aimed to develop a dressing that could effectively aid in the wound healing process and prevent bacterial infections [...] Read more.
Antimicrobial resistance and biofilm formation in diabetic foot infections worsened during the COVID-19 pandemic, resulting in more severe infections and increased amputations. Therefore, this study aimed to develop a dressing that could effectively aid in the wound healing process and prevent bacterial infections by exerting both antibacterial and anti-biofilm effects. Silver nanoparticles (AgNPs) and lactoferrin (LTF) have been investigated as alternative antimicrobial and anti-biofilm agents, respectively, while dicer-substrate short interfering RNA (DsiRNA) has also been studied for its wound healing effect in diabetic wounds. In this study, AgNPs were complexed with LTF and DsiRNA via simple complexation before packaging in gelatin hydrogels. The formed hydrogels exhibited 1668% maximum swellability, with a 46.67 ± 10.33 µm average pore size. The hydrogels demonstrated positive antibacterial and anti-biofilm effects toward the selected Gram-positive and Gram-negative bacteria. The hydrogel containing AgLTF at 125 µg/mL was also non-cytotoxic on HaCaT cells for up to 72 h of incubation. The hydrogels containing DsiRNA and LTF demonstrated superior pro-migratory effects compared to the control group. In conclusion, the AgLTF-DsiRNA-loaded hydrogel possessed antibacterial, anti-biofilm, and pro-migratory activities. These findings provide a further understanding and knowledge on forming multipronged AgNPs consisting of DsiRNA and LTF for chronic wound therapy. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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16 pages, 4174 KiB  
Article
Bovine Lactoferrin Suppresses Tumor Angiogenesis through NF-κB Pathway Inhibition by Binding to TRAF6
by Nurina Febriyanti Ayuningtyas, Chanbora Chea, Toshinori Ando, Karina Erda Saninggar, Keiji Tanimoto, Toshihiro Inubushi, Nako Maishi, Kyoko Hida, Masanobu Shindoh, Mutsumi Miyauchi and Takashi Takata
Pharmaceutics 2023, 15(1), 165; https://doi.org/10.3390/pharmaceutics15010165 - 03 Jan 2023
Cited by 4 | Viewed by 1796
Abstract
Tumor angiogenesis is essential for tumor progression. The inhibition of tumor angiogenesis is a promising therapy for tumors. Bovine lactoferrin (bLF) has been reported as an anti-tumor agent. However, bLF effects on tumor angiogenesis are not well demonstrated. This study evaluated the inhibitory [...] Read more.
Tumor angiogenesis is essential for tumor progression. The inhibition of tumor angiogenesis is a promising therapy for tumors. Bovine lactoferrin (bLF) has been reported as an anti-tumor agent. However, bLF effects on tumor angiogenesis are not well demonstrated. This study evaluated the inhibitory effects of bLF on tumor angiogenesis in vivo and in vitro. Herein, tumor endothelial cells (TECs) and normal endothelial cells (NECs) were used. Proliferation, migration, tube formation assays, RT-PCR, flow cytometry, Western blotting, siRNA experiments and immunoprecipitation were conducted to clarify the mechanisms of bLF-induced effects. CD-31 immunoexpression was examined in tumor tissues of oral squamous cell carcinoma mouse models with or without Liposomal bLF (LbLF)-administration. We confirmed that bLF inhibited proliferation/migration/tube formation and increased apoptosis in TECs but not NECs. TNF receptor-associated factor 6 (TRAF6), p-p65, hypoxia inducible factor-α (HIF-1α) and vascular endothelial growth factor (VEGF) were highly expressed in TECs. In TECs, bLF markedly downregulated VEGF-A, VEGF receptor (VEGFR) and HIF-1α via the inhibition of p-p65 through binding with TRAF6. Since NECs slightly expressed p-p65, bLF–TRAF-6 binding could not induce detectable changes. Moreover, orally administrated LbLF decreased CD31-positive microvascular density only in TECs. Hence, bLF specifically suppressed tumor angiogenesis through p-p65 inhibition by binding to TRAF6 and suppressing HIF-1α activation followed by VEGF/VEGFR down-regulation. Collectively, bLF can be an anti-angiogenic agent for tumors. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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9 pages, 3824 KiB  
Article
Human Recombinant Lactoferrin Promotes Differentiation and Calcification on MC3T3-E1 Cells
by Daichi Nagashima, Yukiko Ishibashi, Sachiko Kawaguchi, Megumi Furukawa, Masahiro Toho, Megumi Ohno, Takeaki Nitto and Nobuo Izumo
Pharmaceutics 2023, 15(1), 60; https://doi.org/10.3390/pharmaceutics15010060 - 25 Dec 2022
Cited by 3 | Viewed by 1504
Abstract
Lactoferrin (LF), known to be present in mammalian milk, has been reported to promote the proliferation of osteoblasts and suppress bone resorption by affecting osteoclasts. However, the mechanisms underlying the effects of human sources LF on osteoblast differentiation have not yet been elucidated, [...] Read more.
Lactoferrin (LF), known to be present in mammalian milk, has been reported to promote the proliferation of osteoblasts and suppress bone resorption by affecting osteoclasts. However, the mechanisms underlying the effects of human sources LF on osteoblast differentiation have not yet been elucidated, and almost studies have used LF from bovine sources. The presented study aimed to characterize the molecular mechanisms of bovine lactoferrin (IF-I) and human recombinant lactoferrin (LF-II) on MC3T3-E1 pre-osteoblast cells. MC3T3-E1 cells were treated with LF, ascorbic acid, and β-glycerophosphate (β-GP). Cell proliferation was analyzed using the MTT assay. Alkaline phosphatase activation and osteopontin expression levels were evaluated via cell staining and immunocytochemistry. The differentiation markers were examined using quantitative real-time PCR. The cell viability assay showed the treatment of 100 μg/mL LF significantly increased; however, it was suppressed by the simultaneous treatment of ascorbic acid and β-GP. Alizarin red staining showed that the 100 μg/mL treatment of LF enhanced calcification. Quantitative real-time PCR showed a significant increase in osterix expression. The results suggest that treatment with both LFs enhanced MC3T3-E1 cell differentiation and promoted calcification. The mechanisms of calcification suggest that LFs are affected by an increase in osterix and osteocalcin mRNA levels. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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24 pages, 4968 KiB  
Article
Sequential Delivery of Novel Triple Drug Combination via Crosslinked Alginate/Lactoferrin Nanohybrids for Enhanced Breast Cancer Treatment
by Mai Salah, Marwa A. Sallam, Mona A. Abdelmoneem, Mohamed Teleb, Kadria A. Elkhodairy, Adnan A. Bekhit, Asmaa F. Khafaga, Ahmed E. Noreldin, Ahmed O. Elzoghby and Sherine N. Khattab
Pharmaceutics 2022, 14(11), 2404; https://doi.org/10.3390/pharmaceutics14112404 - 08 Nov 2022
Cited by 3 | Viewed by 1987
Abstract
While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the [...] Read more.
While breast cancer remains a global health concern, the elaboration of rationally designed drug combinations coupled with advanced biocompatible delivery systems offers new promising treatment venues. Herein, we repurposed rosuvastatin (RST) based on its selective tumor apoptotic effect and combined it with the antimetabolite pemetrexed (PMT) and the tumor-sensitizing polyphenol honokiol (HK). This synergistic three-drug combination was incorporated into protein polysaccharide nanohybrids fabricated by utilizing sodium alginate (ALG) and lactoferrin (LF), inspired by the stealth property of the former and the cancer cell targeting capability of the latter. ALG was conjugated to PMT and then coupled with LF which was conjugated to RST, forming core shell nanohybrids into which HK was physically loaded, followed by cross linking using genipin. The crosslinked HK-loaded PMT–ALG/LF–RST nanohybrids exhibited a fair drug loading of 7.86, 5.24 and 6.11% for RST, PMT and HK, respectively. It demonstrated an eight-fold decrease in the IC50 compared to the free drug combination, in addition to showing an enhanced cellular uptake by MCF-7 cells. The in vivo antitumor efficacy in a breast cancer-bearing mouse model confirmed the superiority of the triple cocktail-loaded nanohybrids. Conclusively, our rationally designed triple drug-loaded protein/polysaccharide nanohybrids offer a promising, biocompatible approach for an effective breast tumor suppression. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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7 pages, 840 KiB  
Communication
Contact Lens Wear Induces Alterations of Lactoferrin Functionality in Human Tears
by Erika Ponzini, Silvia Tavazzi, Giacomo Musile, Franco Tagliaro, Rita Grandori and Carlo Santambrogio
Pharmaceutics 2022, 14(10), 2188; https://doi.org/10.3390/pharmaceutics14102188 - 14 Oct 2022
Cited by 4 | Viewed by 1401
Abstract
The tear film is a complex matrix composed of several molecular classes, from small metal ions to macromolecules. Contact lens (CL) wear can affect the protein homeostasis of the tear film, by accumulating deposits on the CL surface and/or altering their structural and [...] Read more.
The tear film is a complex matrix composed of several molecular classes, from small metal ions to macromolecules. Contact lens (CL) wear can affect the protein homeostasis of the tear film, by accumulating deposits on the CL surface and/or altering their structural and functional properties. This work investigates the effect of CL wear on lactoferrin (Lf), one of the most abundant tear proteins, known as an unspecific biomarker of inflammation. Tears from eight volunteers were collected and analyzed after alternated periods of CL wear and without CL. The experimental approach is to probe Lf into unprocessed human tears by the peculiar fluorescence emission originating from complex formation of Lf with terbium (Tb3+) at the iron-binding sites. The experimental data indicate that CL wear does not significantly affect the total amount of Lf. On the other hand, Lf affinity for Tb3+ is reduced upon CL wear, suggesting relevant changes in Lf structure and possible alterations of protein functionality. Future studies based on this approach will help define CL features (material, lens-care solution, wearing time, etc.) with minimal effects on tear protein activity, in order to obtain more biocompatible and comfortable devices. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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24 pages, 6262 KiB  
Article
Lactoferrin Binding to SARS-CoV-2 Spike Glycoprotein Blocks Pseudoviral Entry and Relieves Iron Protein Dysregulation in Several In Vitro Models
by Antimo Cutone, Luigi Rosa, Maria Carmela Bonaccorsi di Patti, Federico Iacovelli, Maria Pia Conte, Giusi Ianiro, Alice Romeo, Elena Campione, Luca Bianchi, Piera Valenti, Mattia Falconi and Giovanni Musci
Pharmaceutics 2022, 14(10), 2111; https://doi.org/10.3390/pharmaceutics14102111 - 03 Oct 2022
Cited by 10 | Viewed by 2743
Abstract
SARS-CoV-2 causes COVID-19, a predominantly pulmonary disease characterized by a burst of pro-inflammatory cytokines and an increase in free iron. The viral glycoprotein Spike mediates fusion to the host cell membrane, but its role as a virulence factor is largely unknown. Recently, the [...] Read more.
SARS-CoV-2 causes COVID-19, a predominantly pulmonary disease characterized by a burst of pro-inflammatory cytokines and an increase in free iron. The viral glycoprotein Spike mediates fusion to the host cell membrane, but its role as a virulence factor is largely unknown. Recently, the antiviral activity of lactoferrin against SARS-CoV-2 was demonstrated in vitro and shown to occur via binding to cell surface receptors, and its putative interaction with Spike was suggested by in silico analyses. We investigated the anti-SARS-CoV-2 activity of bovine and human lactoferrins in epithelial and macrophagic cells using a Spike-decorated pseudovirus. Lactoferrin inhibited pseudoviral fusion and counteracted the deleterious effects of Spike on iron and inflammatory homeostasis by restoring basal levels of iron-handling proteins and of proinflammatory cytokines IL-1β and IL-6. Using pull-down assays, we experimentally proved for the first time that lactoferrin binds to Spike, immediately suggesting a mechanism for the observed effects. The contribution of transferrin receptor 1 to Spike-mediated cell fusion was also experimentally demonstrated. In silico analyses showed that lactoferrin interacts with transferrin receptor 1, suggesting a multifaceted mechanism of action for lactoferrin. Our results give hope for the use of bovine lactoferrin, already available as a nutraceutical, as an adjuvant to standard therapies in COVID-19. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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14 pages, 2070 KiB  
Article
Lactoferrin Decreases Enterotoxigenic Escherichia coli-Induced Fluid Secretion and Bacterial Adhesion in the Porcine Small Intestine
by Matthias Dierick, Ruben Ongena, Daisy Vanrompay, Bert Devriendt and Eric Cox
Pharmaceutics 2022, 14(9), 1778; https://doi.org/10.3390/pharmaceutics14091778 - 25 Aug 2022
Cited by 7 | Viewed by 2071
Abstract
Enterotoxigenic Escherichia coli (ETEC) infections are one of the most prevalent causes of post-weaning diarrhea in piglets, resulting in morbidity, mortality and elevated use of antibiotics. The emergence and further spread of antimicrobial resistance together with the growing demand for high quality animal [...] Read more.
Enterotoxigenic Escherichia coli (ETEC) infections are one of the most prevalent causes of post-weaning diarrhea in piglets, resulting in morbidity, mortality and elevated use of antibiotics. The emergence and further spread of antimicrobial resistance together with the growing demand for high quality animal protein requires the identification of novel alternatives for antimicrobials. A promising alternative is lactoferrin, as we previously showed that it can both inhibit the growth and degrade bacterial virulence factors of porcine ETEC strains in vitro. Aiming to confirm these findings in vivo, we performed a small intestinal segment perfusion experiment in piglets. Here, we showed that lactoferrin could not only decrease ETEC-induced fluid secretion, but also their ability to colonize the small intestinal epithelium. Furthermore, while ETEC infection induced pro-inflammatory cytokine mRNA expression in this experiment, lactoferrin was not able to counteract these responses. In addition, a bacterial motility assay showed that lactoferrin can reduce the motility of ETEC. Our findings further support the use of lactoferrin as an alternative for antimicrobials and also show its potential for the prevention of ETEC infections in pigs. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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13 pages, 1596 KiB  
Article
Oral Lactoferrin Supplementation during Induction Chemotherapy Promotes Gut Microbiome Eubiosis in Pediatric Patients with Hematologic Malignancies
by Federica D’Amico, Nunzia Decembrino, Edoardo Muratore, Silvia Turroni, Paola Muggeo, Rosamaria Mura, Katia Perruccio, Virginia Vitale, Marco Zecca, Arcangelo Prete, Francesco Venturelli, Davide Leardini, Patrizia Brigidi, Riccardo Masetti, Simone Cesaro and Daniele Zama
Pharmaceutics 2022, 14(8), 1705; https://doi.org/10.3390/pharmaceutics14081705 - 16 Aug 2022
Cited by 10 | Viewed by 2193
Abstract
Induction chemotherapy is the first-line treatment for pediatric patients with hematologic malignancies. However, several complications may arise, mainly infections and febrile neutropenia, with a strong impact on patient morbidity and mortality. Such complications have been shown to be closely related to alterations of [...] Read more.
Induction chemotherapy is the first-line treatment for pediatric patients with hematologic malignancies. However, several complications may arise, mainly infections and febrile neutropenia, with a strong impact on patient morbidity and mortality. Such complications have been shown to be closely related to alterations of the gut microbiome (GM), making the design of strategies to foster its eubiosis of utmost clinical importance. Here, we evaluated the impact of oral supplementation of lactoferrin (LF), a glycoprotein endowed with anti-inflammatory, immunomodulatory and antimicrobial activities, on GM dynamics in pediatric oncohematologic patients during induction chemotherapy. Specifically, we conducted a double blind, placebo-controlled trial in which GM was profiled through 16S rRNA gene sequencing before and after two weeks of oral supplementation with LF or placebo. LF was safely administered with no adverse effects and promoted GM homeostasis by favoring the maintenance of diversity and preventing the bloom of pathobionts (e.g., Enterococcus). LF could, therefore, be a promising adjunct to current therapeutic strategies in these fragile individuals to reduce the risk of GM-related complications. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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Review

Jump to: Research

31 pages, 2978 KiB  
Review
The Role of Lactoferrin in Intestinal Health
by Celia Conesa, Andrea Bellés, Laura Grasa and Lourdes Sánchez
Pharmaceutics 2023, 15(6), 1569; https://doi.org/10.3390/pharmaceutics15061569 - 23 May 2023
Cited by 7 | Viewed by 3562
Abstract
The intestine represents one of the first barriers where microorganisms and environmental antigens come into tight contact with the host immune system. A healthy intestine is essential for the well-being of humans and animals. The period after birth is a very important phase [...] Read more.
The intestine represents one of the first barriers where microorganisms and environmental antigens come into tight contact with the host immune system. A healthy intestine is essential for the well-being of humans and animals. The period after birth is a very important phase of development, as the infant moves from a protected environment in the uterus to one with many of unknown antigens and pathogens. In that period, mother’s milk plays an important role, as it contains an abundance of biologically active components. Among these components, the iron-binding glycoprotein, lactoferrin (LF), has demonstrated a variety of important benefits in infants and adults, including the promotion of intestinal health. This review article aims to provide a compilation of all the information related to LF and intestinal health, in infants and adults. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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18 pages, 2161 KiB  
Review
Lactoferrin and Nanotechnology: The Potential for Cancer Treatment
by Tuan Hiep Tran, Phuong Thi Thu Tran and Duy Hieu Truong
Pharmaceutics 2023, 15(5), 1362; https://doi.org/10.3390/pharmaceutics15051362 - 28 Apr 2023
Cited by 4 | Viewed by 3026
Abstract
Lactoferrin (Lf)—a glycoprotein of the transferrin family—has been investigated as a promising molecule with diverse applications, including infection inhibition, anti-inflammation, antioxidant properties and immune modulation. Along with that, Lf was found to inhibit the growth of cancerous tumors. Owing to unique properties such [...] Read more.
Lactoferrin (Lf)—a glycoprotein of the transferrin family—has been investigated as a promising molecule with diverse applications, including infection inhibition, anti-inflammation, antioxidant properties and immune modulation. Along with that, Lf was found to inhibit the growth of cancerous tumors. Owing to unique properties such as iron-binding and positive charge, Lf could interrupt the cancer cell membrane or influence the apoptosis pathway. In addition, being a common mammalian excretion, Lf offers is promising in terms of targeting delivery or the diagnosis of cancer. Recently, nanotechnology significantly enhanced the therapeutic index of natural glycoproteins such as Lf. Therefore, in the context of this review, the understanding of Lf is summarized and followed by different strategies of nano-preparation, including inorganic nanoparticles, lipid-based nanoparticles and polymer-based nanoparticles in cancer management. At the end of the study, the potential future applications are discussed to pave the way for translating Lf into actual usage. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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30 pages, 2332 KiB  
Review
Time to Kill and Time to Heal: The Multifaceted Role of Lactoferrin and Lactoferricin in Host Defense
by Anna Ohradanova-Repic, Romana Praženicová, Laura Gebetsberger, Tetiana Moskalets, Rostislav Skrabana, Ondrej Cehlar, Gabor Tajti, Hannes Stockinger and Vladimir Leksa
Pharmaceutics 2023, 15(4), 1056; https://doi.org/10.3390/pharmaceutics15041056 - 24 Mar 2023
Cited by 10 | Viewed by 3760
Abstract
Lactoferrin is an iron-binding glycoprotein present in most human exocrine fluids, particularly breast milk. Lactoferrin is also released from neutrophil granules, and its concentration increases rapidly at the site of inflammation. Immune cells of both the innate and the adaptive immune system express [...] Read more.
Lactoferrin is an iron-binding glycoprotein present in most human exocrine fluids, particularly breast milk. Lactoferrin is also released from neutrophil granules, and its concentration increases rapidly at the site of inflammation. Immune cells of both the innate and the adaptive immune system express receptors for lactoferrin to modulate their functions in response to it. On the basis of these interactions, lactoferrin plays many roles in host defense, ranging from augmenting or calming inflammatory pathways to direct killing of pathogens. Complex biological activities of lactoferrin are determined by its ability to sequester iron and by its highly basic N-terminus, via which lactoferrin binds to a plethora of negatively charged surfaces of microorganisms and viruses, as well as to mammalian cells, both normal and cancerous. Proteolytic cleavage of lactoferrin in the digestive tract generates smaller peptides, such as N-terminally derived lactoferricin. Lactoferricin shares some of the properties of lactoferrin, but also exhibits unique characteristics and functions. In this review, we discuss the structure, functions, and potential therapeutic uses of lactoferrin, lactoferricin, and other lactoferrin-derived bioactive peptides in treating various infections and inflammatory conditions. Furthermore, we summarize clinical trials examining the effect of lactoferrin supplementation in disease treatment, with a special focus on its potential use in treating COVID-19. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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25 pages, 3147 KiB  
Review
Biomedical Applications of Lactoferrin on the Ocular Surface
by Uxía Regueiro, Maite López-López, Rubén Varela-Fernández, Francisco Javier Otero-Espinar and Isabel Lema
Pharmaceutics 2023, 15(3), 865; https://doi.org/10.3390/pharmaceutics15030865 - 07 Mar 2023
Cited by 3 | Viewed by 2730
Abstract
Lactoferrin (LF) is a first-line defense protein with a pleiotropic functional pattern that includes anti-inflammatory, immunomodulatory, antiviral, antibacterial, and antitumoral properties. Remarkably, this iron-binding glycoprotein promotes iron retention, restricting free radical production and avoiding oxidative damage and inflammation. On the ocular surface, LF [...] Read more.
Lactoferrin (LF) is a first-line defense protein with a pleiotropic functional pattern that includes anti-inflammatory, immunomodulatory, antiviral, antibacterial, and antitumoral properties. Remarkably, this iron-binding glycoprotein promotes iron retention, restricting free radical production and avoiding oxidative damage and inflammation. On the ocular surface, LF is released from corneal epithelial cells and lacrimal glands, representing a significant percentage of the total tear fluid proteins. Due to its multifunctionality, the availability of LF may be limited in several ocular disorders. Consequently, to reinforce the action of this highly beneficial glycoprotein on the ocular surface, LF has been proposed for the treatment of different conditions such as dry eye, keratoconus, conjunctivitis, and viral or bacterial ocular infections, among others. In this review, we outline the structure and the biological functions of LF, its relevant role at the ocular surface, its implication in LF-related ocular surface disorders, and its potential for biomedical applications. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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13 pages, 1472 KiB  
Review
Lactoferrin-Conjugated Nanoparticles as New Antivirals
by Malgorzata Krzyzowska, Martyna Janicka, Emilia Tomaszewska, Katarzyna Ranoszek-Soliwoda, Grzegorz Celichowski, Jarosław Grobelny and Pawel Szymanski
Pharmaceutics 2022, 14(9), 1862; https://doi.org/10.3390/pharmaceutics14091862 - 03 Sep 2022
Cited by 5 | Viewed by 2231
Abstract
Lactoferrin is an iron-binding glycoprotein with multiple functions in the body. Its activity against a broad spectrum of both DNA and RNA viruses as well as the ability to modulate immune responses have made it of interest in the pharmaceutical and food industries. [...] Read more.
Lactoferrin is an iron-binding glycoprotein with multiple functions in the body. Its activity against a broad spectrum of both DNA and RNA viruses as well as the ability to modulate immune responses have made it of interest in the pharmaceutical and food industries. The mechanisms of its antiviral activity include direct binding to the viruses or its receptors or the upregulation of antiviral responses by the immune system. Recently, much effort has been devoted to the use of nanotechnology in the development of new antivirals. In this review, we focus on describing the antiviral mechanisms of lactoferrin and the possible use of nanotechnology to construct safe and effective new antiviral drugs. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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28 pages, 8762 KiB  
Review
Activity of Apo-Lactoferrin on Pathogenic Protozoa
by Magda Reyes-López, Gerardo Ramírez-Rico, Jesús Serrano-Luna and Mireya de la Garza
Pharmaceutics 2022, 14(8), 1702; https://doi.org/10.3390/pharmaceutics14081702 - 15 Aug 2022
Cited by 3 | Viewed by 2930
Abstract
Parasites and other eventually pathogenic organisms require the ability to adapt to different environmental conditions inside the host to assure survival. Some host proteins have evolved as defense constituents, such as lactoferrin (Lf), which is part of the innate immune system. Lf in [...] Read more.
Parasites and other eventually pathogenic organisms require the ability to adapt to different environmental conditions inside the host to assure survival. Some host proteins have evolved as defense constituents, such as lactoferrin (Lf), which is part of the innate immune system. Lf in its iron-free form (apo-Lf) and its peptides obtained by cleavage with pepsin are microbicides. Parasites confront Lf in mucosae and blood. In this work, the activity of Lf against pathogenic and opportunistic parasites such as Cryptosporidium spp., Eimeria spp., Entamoeba histolytica, Giardia duodenalis, Leishmania spp., Trypanosoma spp., Plasmodium spp., Babesia spp., Toxoplasma gondii, Trichomonas spp., and the free-living but opportunistic pathogens Naegleria fowleri and Acanthamoeba castellani were reviewed. The major effects of Lf could be the inhibition produced by sequestering the iron needed for their survival and the production of oxygen-free radicals to more complicated mechanisms, such as the activation of macrophages to phagocytes with the posterior death of those parasites. Due to the great interest in Lf in the fight against pathogens, it is necessary to understand the exact mechanisms used by this protein to affect their virulence factors and to kill them. Full article
(This article belongs to the Special Issue Lactoferrin in Biomedical Applications)
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