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Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery

Pázmány Péter Catholic University, Faculty of Information Technology and Bionics, Práter u. 50a, H-1083 Budapest, Hungary
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Sci. Pharm. 2019, 87(1), 6; https://doi.org/10.3390/scipharm87010006
Received: 26 January 2019 / Revised: 22 February 2019 / Accepted: 26 February 2019 / Published: 28 February 2019
(This article belongs to the Special Issue New Insights into Drug Delivery and Absorption)
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Abstract

Treatment of certain central nervous system disorders, including different types of cerebral malignancies, is limited by traditional oral or systemic administrations of therapeutic drugs due to possible serious side effects and/or lack of the brain penetration and, therefore, the efficacy of the drugs is diminished. During the last decade, several new technologies were developed to overcome barrier properties of cerebral capillaries. This review gives a short overview of the structural elements and anatomical features of the blood–brain barrier. The various in vitro (static and dynamic), in vivo (microdialysis), and in situ (brain perfusion) blood–brain barrier models are also presented. The drug formulations and administration options to deliver molecules effectively to the central nervous system (CNS) are presented. Nanocarriers, nanoparticles (lipid, polymeric, magnetic, gold, and carbon based nanoparticles, dendrimers, etc.), viral and peptid vectors and shuttles, sonoporation and microbubbles are briefly shown. The modulation of receptors and efflux transporters in the cell membrane can also be an effective approach to enhance brain exposure to therapeutic compounds. Intranasal administration is a noninvasive delivery route to bypass the blood–brain barrier, while direct brain administration is an invasive mode to target the brain region with therapeutic drug concentrations locally. Nowadays, both technological and mechanistic tools are available to assist in overcoming the blood–brain barrier. With these techniques more effective and even safer drugs can be developed for the treatment of devastating brain disorders. View Full-Text
Keywords: structure of the blood–brain barrier; models of the blood–brain barrier; drug delivery across the blood–brain barrier; nanocarriers; nanoparticles; vectors; intranasal delivery; efflux transporter inhibition; ultrasound-microbubbles structure of the blood–brain barrier; models of the blood–brain barrier; drug delivery across the blood–brain barrier; nanocarriers; nanoparticles; vectors; intranasal delivery; efflux transporter inhibition; ultrasound-microbubbles
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Bors, L.A.; Erdő, F. Overcoming the Blood–Brain Barrier. Challenges and Tricks for CNS Drug Delivery. Sci. Pharm. 2019, 87, 6.

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