Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

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Abstract

The blood–brain barrier (BBB) is a critical biological structure that prevents damage to the brain and maintains its bathing microenvironment. However, this barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases. Many efforts have been made for improvement of delivering drugs across the BBB in recent years to treat CNS diseases. In this review, the anatomical and functional structure of the BBB is comprehensively discussed. The mechanisms of BBB penetration are summarized, and the methods and effects on increasing BBB permeability are investigated in detail. It also elaborates on the physical, chemical, biological and nanocarrier aspects to improve drug delivery penetration to the brain and introduces some specific drug delivery effects on BBB permeability.

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Most cited references 97

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Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability.

Ben Booth, Nick Dunstone, Paul Halloran … (2012)

Systematic climate shifts have been linked to multidecadal variability in observed sea surface temperatures in the North Atlantic Ocean. These links are extensive, influencing a range of climate processes such as hurricane activity and African Sahel and Amazonian droughts. The variability is distinct from historical global-mean temperature changes and is commonly attributed to natural ocean oscillations. A number of studies have provided evidence that aerosols can influence long-term changes in sea surface temperatures, but climate models have so far failed to reproduce these interactions and the role of aerosols in decadal variability remains unclear. Here we use a state-of-the-art Earth system climate model to show that aerosol emissions and periods of volcanic activity explain 76 per cent of the simulated multidecadal variance in detrended 1860-2005 North Atlantic sea surface temperatures. After 1950, simulated variability is within observational estimates; our estimates for 1910-1940 capture twice the warming of previous generation models but do not explain the entire observed trend. Other processes, such as ocean circulation, may also have contributed to variability in the early twentieth century. Mechanistically, we find that inclusion of aerosol-cloud microphysical effects, which were included in few previous multimodel ensembles, dominates the magnitude (80 per cent) and the spatial pattern of the total surface aerosol forcing in the North Atlantic. Our findings suggest that anthropogenic aerosol emissions influenced a range of societally important historical climate events such as peaks in hurricane activity and Sahel drought. Decadal-scale model predictions of regional Atlantic climate will probably be improved by incorporating aerosol-cloud microphysical interactions and estimates of future concentrations of aerosols, emissions of which are directly addressable by policy actions.

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Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging.

Omid Veiseh, Jonathan W. Gunn, Miqin Zhang (2010)

Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties. Copyright 2009 Elsevier B.V. All rights reserved.

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Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer.

Yogeshkumar Malam, Marilena Loizidou, Alexander M. Seifalian (2009)

Nanoscale drug delivery systems using liposomes and nanoparticles are emerging technologies for the rational delivery of chemotherapeutic drugs in the treatment of cancer. Their use offers improved pharmacokinetic properties, controlled and sustained release of drugs and, more importantly, lower systemic toxicity. The commercial availability of liposomal Doxil and albumin-nanoparticle-based Abraxane has focused attention on this innovative and exciting field. Recent advances in liposome technology offer better treatment of multidrug-resistant cancers and lower cardiotoxicity. Nanoparticles offer increased precision in chemotherapeutic targeting of prostate cancer and new avenues for the treatment of breast cancer. Here we review current knowledge on the two technologies and their potential applications to cancer treatment.

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Author and article information

Journal

Journal ID (nlm-ta): Cells

Journal ID (iso-abbrev): Cells

Journal ID (publisher-id): cells

Title: Cells

Publisher: MDPI

ISSN (Electronic): 2073-4409

Publication date (Electronic): 23 March 2018

Publication date Collection: April 2018

Volume: 7

Issue: 4

Electronic Location Identifier: 24

Affiliations

School of Life Science and Chemistry, Hunan University of Technology, Zhuzhou 412007, China; hequanguo@ 123456126.com (Q.H.); liu.jun.1015@ 123456163.com (J.L.); liangjingabbey@ 123456126.com (J.L.); amituo321@ 123456163.com (X.L.); liuzhi0910@ 123456163.com (Z.L.); dingziyu0320@ 123456163.com (Z.D.); dutuo99@ 123456hut.edu.cn (D.T.)

Author notes

[* ]Correspondence: liwendream@ 123456163.com ; Tel.: +86-0731-2218-3882

[†]

These authors contributed equally to this work.

Article

Publisher ID: cells-07-00024

DOI: 10.3390/cells7040024

PMC ID: 5946101

PubMed ID: 29570659

SO-VID: 64edcbc0-62b5-4912-bfa9-d378c0a9fdb4

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

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Abstract

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Nanoparticles to cross the blood-brain barrier (BBB)

Most cited references 97

Aerosols implicated as a prime driver of twentieth-century North Atlantic climate variability.

Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging.

Liposomes and nanoparticles: nanosized vehicles for drug delivery in cancer.

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