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Review
. 2018 Mar 23;7(4):24.
doi: 10.3390/cells7040024.

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

Quanguo He  1 , Jun Liu  2 , Jing Liang  3 , Xiaopeng Liu  4 , Wen Li  5 , Zhi Liu  6 , Ziyu Ding  7 , Du Tuo  8
Affiliations
Review

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

Quanguo He et al. Cells. .

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.

Keywords: blood–brain barrier; central nervous system; diseases; drug delivery system to brain; permeability improvements.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schematic representation of the structure of blood–brain barrier (BBB) (BL1 is basal lamina 1, BL2 is basal lamina 2). Reprinted with permission from ref. [11].
Figure 2
Figure 2
Illustration of the chemical drug delivery system. Reprinted with permission from ref. [31].
Figure 3
Figure 3
Illustration of increasing the cerebral concentration of γ-secretase inhibitors by chemical drug delivery systems. (A) The concentration of drugs in brain 240 ng/g; (B) the concentration of drugs in brain 345 ng/g. Reprinted with permission from ref. [39].
Figure 4
Figure 4
A schematic diagram of the pathway across the BBB. (a) The tight junctions for penetration of water-soluble drugs; (b) the diffusive route for lipid-soluble agents; (c) the carrier-mediated transcytosis (CMT) and (d) active efflux transcytosis; (e) specific receptor-mediated transcytosis (RMT); (f) adsorptive-mediated transcytosis (AMT); (g) tight junction (TJ) modulation. Reprinted with permission from ref. [45].
Figure 5
Figure 5
Schematic of the transmembrane structural organization of human P-glycoprotein (P-gp, 1280 amino acids long). Reprinted with permission from ref. [51].
Figure 6
Figure 6
Schematic diagram of immunoliposomes (ILs).
Figure 7
Figure 7
Type of polymer nanoparticles. Reprinted with permission from ref. [78].
See this image and copyright information in PMC

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