Blood-Brain Delivery Methods Using Nanotechnology
Abstract
:1. Introduction
2. The Blood-Brain Barrier
2.1. The Anatomical Structure of the Blood-Brain Barrier
2.2. The Physiology of the Blood-Brain Barrier
3. Nanotechnology Approaches for Crossing the Blood-Brain Barrier
3.1. Organic Nanomaterials
3.1.1. Polymeric Nanoparticles
3.1.2. Liposomes
3.1.3. Dendrimers
3.1.4. Micelles
3.2. Inorganic Nanomaterials
3.2.1. Gold Nanoparticles
3.2.2. Silica Nanoparticles
3.2.3. Carbon Nanotubes
4. Conclusions and Perspectives
Author Contributions
Funding
Conflicts of Interest
References
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Blood-Brain Barrier Component | Function | |
---|---|---|
Neurovascular unit | endothelial cells | barrier function, transport of micronutrients and macronutrients, receptor-mediated signaling, leukocyte trafficking, and osmoregulation [31] |
astrocytes | responsible for proper neuron and neurovascular unit functions and modulation of the blood-brain barrier phenotype [31] regulation of metabolism, the modulation of neuronal transmission, and brain development and repair [22] | |
pericytes | regulation of endothelial cell proliferation, survival, migration, differentiation, and vascular branching [31] involved in angiogenesis, maintenance of the blood-brain barrier, regulation of immune cell entry to the brain, control of the cerebral blood flow, and constriction of capillaries in stroke [28] | |
neurons | modulation of the blood-brain barrier permeability through neuronal-microvascular communications [31] | |
extracellular matrix | modulation of the blood-brain barrier permeability and maintenance of tight junctions [31] | |
Junctional complexes | occludin | ensures a high electrical resistance (tightness) of the tight junctions [31] |
claudins | primary barrier function of the tight junctions [31] | |
junctional adhesion molecules | mediation of the early attachment of adjacent cell membranes, involved in developmental processes [31] | |
membrane-associated guanylate kinase-like proteins | modulation of the blood-brain barrier permeability [31] |
Nano-Carrier | Diameter (nm) | Surface Charge (mV) | Cellular Uptake (%) | ||
---|---|---|---|---|---|
Organic nanomaterials | Polymeric nanoparticles | poly(lactide-co-glycolic) acid | 200–250 | (−22)–(−13) | 75 [41] |
120 114 143 | −11.6 −14.9 −30.8 | n.r. 90 90 [42] | |||
115 | −17.4 | 17.46 [43,44] | |||
poly(ethylene imine) | 104–160 277–287 116–118 | 28.4 −6.9 33.2 | ~100 <10 ~100 [43,44] | ||
poly(ethylene imine)-poly(l-lysine) copolymer | 136 | 30 | n.r. [45] | ||
poly(allylamine) hydrochloride | 106.5–113.5 | n.r. | n.r. [46] | ||
human serum albumin | 221.9–228.3 | −12.3 | n.r. [47] | ||
polyethylcyanoacrylate | 218–241.1 | (−3.85)–(−2.78) | n.r. [47] | ||
chitosan | 300–324 | 0.584 | n.r. [48] | ||
Liposomes | 173.45–182.79 | 0.56−3.68 | 60–70 [49] | ||
105–110 | (−5)–(−2) | 70–90 [50] | |||
158.7–165.05 | 7.66 | 65–70 [51] | |||
189.21–203.39 | −22.23 | n.r. [52] | |||
Dendrimers | polyamidoamine | 5.1–8.2 | 2.07–3.15 | n.r. [53] | |
poly(propyleneimine) | 37.8–47.6 | 18.2 | n.r. [54] | ||
Micelles | 11.7–24.9 | −30–20 | n.r. [55] | ||
74.2 | −30.25 | n.r. [56] | |||
28.79 | −6.46 | n.r. [57] | |||
Inorganic nanomaterials | Gold nanoparticles | 1.4–60.2 | −64–56 | n.r. [50] | |
Silica nanoparticles | 120–128 | n.r. | n.r. [58] | ||
Carbon nanotubes | 125–296 | n.r. | n.r. [59,60] |
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Teleanu, D.M.; Chircov, C.; Grumezescu, A.M.; Volceanov, A.; Teleanu, R.I. Blood-Brain Delivery Methods Using Nanotechnology. Pharmaceutics 2018, 10, 269. https://doi.org/10.3390/pharmaceutics10040269
Teleanu DM, Chircov C, Grumezescu AM, Volceanov A, Teleanu RI. Blood-Brain Delivery Methods Using Nanotechnology. Pharmaceutics. 2018; 10(4):269. https://doi.org/10.3390/pharmaceutics10040269
Chicago/Turabian StyleTeleanu, Daniel Mihai, Cristina Chircov, Alexandru Mihai Grumezescu, Adrian Volceanov, and Raluca Ioana Teleanu. 2018. "Blood-Brain Delivery Methods Using Nanotechnology" Pharmaceutics 10, no. 4: 269. https://doi.org/10.3390/pharmaceutics10040269