Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics
Transport of macromolecules across the blood-brain-barrier (BBB) requires both specific and nonspecific interactions between macromolecules and proteins/receptors expressed on the luminal and/or the abluminal surfaces of the brain capillary endothelial cells. Endocytosis and transcytosis play import...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | International Journal of Cell Biology |
| Online Access: | http://dx.doi.org/10.1155/2013/703545 |
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| _version_ | 1832554626355822592 |
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| author | Guangqing Xiao Liang-Shang Gan |
| author_facet | Guangqing Xiao Liang-Shang Gan |
| author_sort | Guangqing Xiao |
| collection | DOAJ |
| description | Transport of macromolecules across the blood-brain-barrier (BBB) requires both specific and nonspecific interactions between macromolecules and proteins/receptors expressed on the luminal and/or the abluminal surfaces of the brain capillary endothelial cells. Endocytosis and transcytosis play important roles in the distribution of macromolecules. Due to the tight junction of BBB, brain delivery of traditional therapeutic proteins with large molecular weight is generally not possible. There are multiple pathways through which macromolecules can be taken up into cells through both specific and nonspecific interactions with proteins/receptors on the cell surface. This review is focused on the current knowledge of receptor-mediated endocytosis/transcytosis and brain delivery using the Angiopep-2-conjugated system and the molecular Trojan horses. In addition, the role of neonatal Fc receptor (FcRn) in regulating the efflux of Immunoglobulin G (IgG) from brain to blood, and approaches to improve the pharmacokinetics of therapeutic biologics by generating Fc fusion proteins, and increasing the pH dependent binding affinity between Fc and FcRn, are discussed. |
| format | Article |
| id | doaj-art-377bf2cc2307436aa210ae4c89096df8 |
| institution | Kabale University |
| issn | 1687-8876 1687-8884 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Cell Biology |
| spelling | doaj-art-377bf2cc2307436aa210ae4c89096df82025-02-03T05:50:59ZengWileyInternational Journal of Cell Biology1687-88761687-88842013-01-01201310.1155/2013/703545703545Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic BiologicsGuangqing Xiao0Liang-Shang Gan1Drug Metabolism and Pharmacokinetics, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USADrug Metabolism and Pharmacokinetics, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142, USATransport of macromolecules across the blood-brain-barrier (BBB) requires both specific and nonspecific interactions between macromolecules and proteins/receptors expressed on the luminal and/or the abluminal surfaces of the brain capillary endothelial cells. Endocytosis and transcytosis play important roles in the distribution of macromolecules. Due to the tight junction of BBB, brain delivery of traditional therapeutic proteins with large molecular weight is generally not possible. There are multiple pathways through which macromolecules can be taken up into cells through both specific and nonspecific interactions with proteins/receptors on the cell surface. This review is focused on the current knowledge of receptor-mediated endocytosis/transcytosis and brain delivery using the Angiopep-2-conjugated system and the molecular Trojan horses. In addition, the role of neonatal Fc receptor (FcRn) in regulating the efflux of Immunoglobulin G (IgG) from brain to blood, and approaches to improve the pharmacokinetics of therapeutic biologics by generating Fc fusion proteins, and increasing the pH dependent binding affinity between Fc and FcRn, are discussed.http://dx.doi.org/10.1155/2013/703545 |
| spellingShingle | Guangqing Xiao Liang-Shang Gan Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics International Journal of Cell Biology |
| title | Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics |
| title_full | Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics |
| title_fullStr | Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics |
| title_full_unstemmed | Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics |
| title_short | Receptor-Mediated Endocytosis and Brain Delivery of Therapeutic Biologics |
| title_sort | receptor mediated endocytosis and brain delivery of therapeutic biologics |
| url | http://dx.doi.org/10.1155/2013/703545 |
| work_keys_str_mv | AT guangqingxiao receptormediatedendocytosisandbraindeliveryoftherapeuticbiologics AT liangshanggan receptormediatedendocytosisandbraindeliveryoftherapeuticbiologics |