FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review

Fieux, M.; Quellec, Sandra Le; Bartier, S.; Coste, A.; Louis, Bruno; Giroudon, Caroline; Nourredine, Mikaïl; Béquignon, E.

doi:10.3390/ijms22126475

Cited by 11 publications

(6 citation statements)

References 117 publications

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“…FcRn is widely distributed in many tissues and cell types including vascular, renal (podocytes and the proximal convoluted tubule) and brain endothelia; antigen-presenting cells; and gut, upper airway and alveolar epithelia. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest [ 19 ]. Also, FcRn is required for the delivery of newly synthesized albumin to the basolateral side of cells and subsequent secretion of albumin into the bloodstream.…”

Section: Introduction: Historical Aspects Origin and Destination And Evolutionary And Genetic Features Of Albuminmentioning

confidence: 99%

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Belinskaia

Voronina

Шмурак

et al. 2021

IJMS

142

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Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions—electrically neutral and charged molecules—and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

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Section: Introduction: Historical Aspects Origin and Destination And Evolutionary And Genetic Features Of Albuminmentioning

confidence: 99%

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Belinskaia

Voronina

Шмурак

et al. 2021

IJMS

142

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“…This indicates that, as previously suggested [ 10 ], the reduced T cell activation and proliferation is the critical mechanism by which ALCAM blockade reduces inflammatory symptoms in OVA-induced asthma. Interestingly, the neonatal Fc receptor (FcRN) has been suggested to support the transport of Fc-containing antibodies across the nasal epithelium [ 19 , 70 , 71 ]. Fc-mediated active transepithelial uptake might therefore have additionally enhanced the in vivo activity of intranasally administered IF8-Fc and compensated for the fact that IF8-Fc was administered at a four times lower molar concentration during equimass treatment compared to scFv V2D7.…”

Section: Discussionmentioning

confidence: 99%

Optimization and Characterization of Novel ALCAM-Targeting Antibody Fragments for Transepithelial Delivery

Bauer,

Klassa,

Herbst

et al. 2023

Pharmaceutics

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Activated leukocyte cell adhesion molecule (ALCAM) is a cell adhesion molecule that supports T cell activation, leukocyte migration, and (lymph)angiogenesis and has been shown to contribute to the pathology of various immune-mediated disorders, including asthma and corneal graft rejection. In contrast to monoclonal antibodies (mAbs) targeting ALCAM’s T cell expressed binding partner CD6, no ALCAM-targeting mAbs have thus far entered clinical development. This is likely linked with the broad expression of ALCAM on many different cell types, which increases the risk of eliciting unwanted treatment-induced side effects upon systemic mAb application. Targeting ALCAM in surface-exposed tissues, such as the lungs or the cornea, by a topical application could circumvent this issue. Here, we report the development of various stability- and affinity-improved anti-ALCAM mAb fragments with cross-species reactivity towards mouse, rat, monkey, and human ALCAM. Fragments generated in either mono- or bivalent formats potently blocked ALCAM–CD6 interactions in a competition ELISA, but only bivalent fragments efficiently inhibited ALCAM–ALCAM interactions in a leukocyte transmigration assay. The different fragments displayed a clear size-dependence in their ability to penetrate the human corneal epithelium. Furthermore, intranasal delivery of anti-ALCAM fragments reduced leukocyte infiltration in a mouse model of asthma, confirming ALCAM as a target for topical application in the lungs.

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“…Following endocytosis in epithelial cells, immunoglobulin G (IgG) and albumin bind to the neonatal fragment crystallizable receptor (FcRn) in endosomes, triggering transcytosis and release at the apical surface 141 . Fusing therapeutic proteins with Fc domains or albumin promotes uptake at the mucosal surface 142 (Fig. 6a).…”

Section: Delivery At Mucosal Barriersmentioning

confidence: 99%

Targeted modulation of immune cells and tissues using engineered biomaterials

Yousefpour

Irvine

2023

Nat Rev Bioeng

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system. We focus on approaches targeting immune cells and lymphoid organs, excluding direct targeting of pathogens such as viruses or bacteria, followed by a discussion on prospects and challenges for developments in this area. Targeting lymphoid organsLymphoid organs coordinate the maturation and migration of immune cells while organizing and regulating immune responses (Fig. 1a). Primary lymphoid organs in adults include the bone marrow and thymus, which serve as niches for lymphocyte development. Secondary lymphoid organs -which include 600-800 lymph nodes distributed across the body, the spleen and the mucosa-associated lymphoid tissue -house and organize T cells, B cells and antigen-presenting cells (APCs). These organs serve as command centres of adaptive immunity where activation of naive B and T lymphocytes occurs (Fig. 1a,b) and are thus natural targets for vaccines and immunotherapies. Principles of lymph node targetingPassive targeting of therapeutics to lymphatic vessels. Lymph nodes interface with peripheral tissues through lymphatic vessels, which drain lymph fluid from all tissues and provide a conduit for immune cell trafficking. Drugs and vaccines can be targeted to lymph nodes through lymphatic uptake following parenteral injection. A major factor influencing lymphatic targeting is the physical size of the injected agents: following injection into tissue (including tumours), particles larger than 50-100 nm in diameter become trapped in the extracellular matrix (ECM), whereas particles in the size range of 5-50 nm convect with lymph into the lymphatic vessels and flow to draining lymph nodes (dLNs). By contrast, particles smaller than 5 nm partition preferentially into the blood rather than the lymph 9,10 (Fig. 2a). These approximate size ranges depend on the tissue site of injection (which can vary in ECM and lymphatic composition) and factors such as injection volume and rate (which can cause mechanical expansion of the flaps mediating entry into lymphatic vessels), especially in small-animal models, where tissue volume relative to injection volume is much smaller. Furthermore, particle shape, charge and surface chemistry can also play a part by promoting or hindering convection through the tissue and lymphatic entry 11 . Notably, capture of particles at the downstream dLN is a less studied but equally important prerequisite for lymph node modulation, as evidenced by data showing that proteins 12 and small hydrophilic nanoparticles 13 can pass through the entire lymphatic chain, reach the thoracic duct and enter the systemic circulation following a parenteral injection. In this regard, using adjuvants that promote compound entry into lymph nodes 14 , or designing carriers that stimulate recognition by macrophages lining the subcapsular and medullary sinuses, can prove useful 15 .Protein nanoparticles with surface-arrayed antigens and a size optimized for efficient lymphatic uptake enhance the immunogenicity of vaccines [16][17][18][19][20] . Protein nanoparticle vaccines are currently in clinic...

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FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review

Cited by 11 publications

References 117 publications

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

Optimization and Characterization of Novel ALCAM-Targeting Antibody Fragments for Transepithelial Delivery

Targeted modulation of immune cells and tissues using engineered biomaterials

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