<abstract xmlns="http://www.w3.org/1999/xhtml"><p>The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the central nervous system. Many potential drugs, which are effective at their site of action, have failed due to the lack of distribution in sufficient quantity to the central nervous system (CNS). In consequence, many diseases of the central nervous system remain undertreated. Antibodies, IgG for example, are difficult to deliver to the CNS due to their size (~155 kDa), physico-chemical properties and the presence of Fc receptor on the blood-brain barrier. Smaller antibodies, like the recently developed nanobodies, may overcome the obstacle of the BBB and enter into the CNS. The nanobodies are the smallest available antigen-binding fragments harbouring the full antigenbinding capacity of conventional antibodies. They represent a new generation of therapeutics with exceptional properties, such as: recognition of unique epitopes, target specificity, high affinity, high solubility, high stability and high expression yields in cost-effective recombinant production. Their ability to permeate across the BBBmakes thema promising alternative for central nervous system disease therapeutics. In this review, we have systematically presented different aspects of the BBB, drug delivery mechanisms employed to cross the BBB, and finally nanobodies — a potential therapeutic molecule against neuroinfections.</p></abstract>

The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the central nervous system. Many potential drugs, which are effective at their site of action, have failed due to the lack of distribution in sufficient quantity to the central nervous system (CNS). In consequence, many diseases of the central nervous system remain undertreated. Antibodies, IgG for example, are difficult to deliver to the CNS due to their size (~155 kDa), physico-chemical properties and the presence of Fc receptor on the blood-brain barrier. Smaller antibodies, like the recently developed nanobodies, may overcome the obstacle of the BBB and enter into the CNS. The nanobodies are the smallest available antigen-binding fragments harbouring the full antigenbinding capacity of conventional antibodies. They represent a new generation of therapeutics with exceptional properties, such as: recognition of unique epitopes, target specificity, high affinity, high solubility, high stability and high expression yields in cost-effective recombinant production. Their ability to permeate across the BBBmakes thema promising alternative for central nervous system disease therapeutics. In this review, we have systematically presented different aspects of the BBB, drug delivery mechanisms employed to cross the BBB, and finally nanobodies — a potential therapeutic molecule against neuroinfections.

Permeability of the Blood-Brain Barrier and Transport of Nanobodies Across the Blood-Brain Barrier

Laboratory of Biomedical Microbiology and Immunology

University of Veterinary Medicine and Pharmacy

Institute of Neuroimmunology, Slovak Academy of Sciences

Folia Veterinaria

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the...

Permeability of the Blood-Brain Barrier and Transport of Nanobodies Across the Blood-Brain Barrier

Online veröffentlicht: 11. Apr. 2018

Seitenbereich: 59 - 66

Eingereicht: 04. Dez. 2017

Akzeptiert: 26. Jan. 2018

DOI: https://doi.org/10.2478/fv-2018-0009

Schlüsselwörter
blood-brain barrier, carrier, nanobody, permeability, shuttle, transport

© 2018 Širochmanová, I. et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Permeability of the Blood-Brain Barrier and Transport of Nanobodies Across the Blood-Brain Barrier

Online veröffentlicht: 11. Apr. 2018

Seitenbereich: 59 - 66

Eingereicht: 04. Dez. 2017

Akzeptiert: 26. Jan. 2018

DOI: https://doi.org/10.2478/fv-2018-0009

Schlüsselwörterblood-brain barrier, carrier, nanobody, permeability, shuttle, transport

© 2018 Širochmanová, I. et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Schlüsselwörter
blood-brain barrier, carrier, nanobody, permeability, shuttle, transport