Abstract
The blood-brain barrier (BBB) is considered an important protective barrier in the central nervous system (CNS). The barrier is mainly formed by endothelial cells (ECs) interconnected by various junctions such as tight junctions (TJs), gap junctions, and adherent junctions. They collectively constitute an intensive barrier to the transit of different substances into the brain, selectively permitting small molecules to pass through by passive movement but holding off large ones such as peptides and proteins to cross the brain. Hence some molecules selectively transfer across the BBB by active routes via transcytosis. The BBB also forms a barrier against neurotoxins as well as pathogenic agents. Although various CNS disorders like Alzheimer's disease (AD) and Parkinson's disease (PD) could hamper the integrity of the border. Nevertheless, the BBB acts as a barrier for CNS disorders treatment because it prevents the drugs from reaching their target in the CNS. In recent years, different strategies, including osmotic disruption of BBB or chemical modification of drugs, have been used to transfer the chemotherapeutic agents into brain substances. Nowadays, nanoparticles (NPs) have been used as an effective and non-invasive tool for drug delivery and diagnosis of CNS disorders. In this review, we discuss the structural characteristic of BBB, safe passageways to cross the BBB, and the relation of barrier lesions with different CNS disorders. In the end, we explore the progress in drug delivery, diagnosis, imaging, and treatment of CNS disorders using nanoparticles.
Keywords: Blood-brain barrier, CNS, nanoparticles, nanodelivery, drug targets, drug delivery.
Graphical Abstract
[http://dx.doi.org/10.1038/nrn3114] [PMID: 22048062]
[http://dx.doi.org/10.1038/nn.2946] [PMID: 22030551]
[http://dx.doi.org/10.1038/nrn2995] [PMID: 21331083]
[http://dx.doi.org/10.1002/glia.20990] [PMID: 20468051]
[http://dx.doi.org/10.1215/S1152851705000232] [PMID: 16212810]
[http://dx.doi.org/10.1016/j.neuint.2012.08.017] [PMID: 22982300]
[http://dx.doi.org/10.1038/nrn1824] [PMID: 16371949]
[http://dx.doi.org/10.1016/j.pneurobio.2019.04.001] [PMID: 30954517]
[http://dx.doi.org/10.1126/science.1067122] [PMID: 12065827]
[http://dx.doi.org/10.1016/j.nbd.2009.07.030] [PMID: 19664713]
[http://dx.doi.org/10.1016/j.addr.2010.08.004] [PMID: 20709124]
[http://dx.doi.org/10.1186/s13036-017-0076-1] [PMID: 29213304]
[PMID: 1616050]
[http://dx.doi.org/10.1146/annurev.neuro.22.1.11] [PMID: 10202530]
[http://dx.doi.org/10.1096/fj.07-8319com] [PMID: 17761522]
[http://dx.doi.org/10.2174/138920112803341851] [PMID: 23016640]
[http://dx.doi.org/10.1023/A:1007026504843] [PMID: 10696507]
[PMID: 2994489]
[http://dx.doi.org/10.1016/j.ijpharm.2018.04.062] [PMID: 29715532]
[http://dx.doi.org/10.1016/j.colsurfb.2016.04.041] [PMID: 27131092]
[http://dx.doi.org/10.1016/j.neuron.2013.10.061] [PMID: 24411731]
[http://dx.doi.org/10.1007/s11095-007-9357-6] [PMID: 17602284]
[http://dx.doi.org/10.3389/fnins.2018.01019] [PMID: 30686985]
[http://dx.doi.org/10.1002/bit.21120] [PMID: 16937408]
[http://dx.doi.org/10.1080/10623320802487759] [PMID: 19065317]
[http://dx.doi.org/10.1096/fj.201600827R] [PMID: 28108572]
[http://dx.doi.org/10.1046/j.1471-4159.2002.01201.x] [PMID: 12421365]
[http://dx.doi.org/10.1038/sj.gt.3302888] [PMID: 17167498]
[http://dx.doi.org/10.1038/nature13241] [PMID: 24828044]
[http://dx.doi.org/10.1074/jbc.M116.721035] [PMID: 26945070]
[http://dx.doi.org/10.1038/ng.3313] [PMID: 26005865]
[http://dx.doi.org/10.1038/ng.3311] [PMID: 26005868]
[PMID: 28974108]
[http://dx.doi.org/10.1016/j.addr.2019.11.009] [PMID: 31790711]
[http://dx.doi.org/10.1161/JAHA.117.005811] [PMID: 28724654]
[http://dx.doi.org/10.1038/nature13324] [PMID: 24828040]
[http://dx.doi.org/10.1016/j.phrs.2015.12.024] [PMID: 26747400]
[http://dx.doi.org/10.1021/ar200106e] [PMID: 21919457]
[http://dx.doi.org/10.1021/acs.jpcc.5b11232]
[http://dx.doi.org/10.1021/ar800035u] [PMID: 18712884]
[http://dx.doi.org/10.1016/j.addr.2008.03.016] [PMID: 18555555]
[http://dx.doi.org/10.1259/bjr/59448833] [PMID: 22010024]
[http://dx.doi.org/10.1021/ja078176p] [PMID: 18407638]
[http://dx.doi.org/10.1038/nm.2721] [PMID: 22504484]
[http://dx.doi.org/10.1016/j.biomaterials.2007.12.037] [PMID: 18242692]
[http://dx.doi.org/10.1039/C3NR04878K] [PMID: 24362586]
[http://dx.doi.org/10.1093/toxsci/kfv176] [PMID: 26272951]
[http://dx.doi.org/10.1039/b806051g] [PMID: 19587967]
[http://dx.doi.org/10.1038/nbt1171] [PMID: 16333296]
[http://dx.doi.org/10.1007/s003300100908] [PMID: 11702180]
[http://dx.doi.org/10.1016/j.addr.2006.09.013] [PMID: 17116343]
[http://dx.doi.org/10.1038/jcbfm.2009.192] [PMID: 19756021]
[http://dx.doi.org/10.1227/01.NEU.0000255350.71700.37] [PMID: 17415196]
[http://dx.doi.org/10.1021/nn300240p] [PMID: 22443607]
[http://dx.doi.org/10.1016/j.nano.2011.08.017] [PMID: 21930108]
[http://dx.doi.org/10.1021/cr100449n] [PMID: 22204603]
[http://dx.doi.org/10.2174/1874764710801010034]
[http://dx.doi.org/10.1016/j.actbio.2015.03.013] [PMID: 25792279]
[http://dx.doi.org/10.1016/j.ejps.2016.02.012] [PMID: 26924227]
[http://dx.doi.org/10.1007/s11051-009-9661-7]
[http://dx.doi.org/10.1371/journal.pone.0021857] [PMID: 21747962]
[PMID: 14678964]
[http://dx.doi.org/10.1016/j.nbd.2009.07.028] [PMID: 19664710]
[http://dx.doi.org/10.1039/b915139g] [PMID: 20697629]
[http://dx.doi.org/10.1039/c3an36705c] [PMID: 23518695]
[http://dx.doi.org/10.1021/ja040082h] [PMID: 15469243]
[http://dx.doi.org/10.1039/C4TC00988F]
[http://dx.doi.org/10.1016/j.biopha.2016.12.108] [PMID: 28061404]
[http://dx.doi.org/10.1016/j.colsurfb.2016.05.007] [PMID: 27187189]
[http://dx.doi.org/10.1016/j.jconrel.2017.12.015]
[http://dx.doi.org/10.1021/ac303113n] [PMID: 23214718]
[http://dx.doi.org/10.1002/adma.201200650] [PMID: 22718562]
[http://dx.doi.org/10.1002/smll.201402648] [PMID: 25521301]
[http://dx.doi.org/10.1039/c2jm35592b]
[http://dx.doi.org/10.1016/S0045-7949(96)00201-5]
[http://dx.doi.org/10.1093/acprof:oso/9780198717478.001.0001]
[http://dx.doi.org/10.1134/S1063785006010238]
[http://dx.doi.org/10.1002/adma.201405070] [PMID: 25589141]
[http://dx.doi.org/10.1016/j.carbon.2012.12.074]
[http://dx.doi.org/10.1002/anie.200900652] [PMID: 19388019]