Abstract
The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in-situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.
Keywords: Alzheimer’s, blood-brain barrier, poloxamer, thermo-responsive, in-situ gel, chitosan.
[http://dx.doi.org/10.1155/2014/869269] [PMID: 25136634]
[http://dx.doi.org/10.1136/bmj.m3683] [PMID: 33037002]
[http://dx.doi.org/10.1371/journal.pone.0136271] [PMID: 26352911]
[http://dx.doi.org/10.2217/nnm-2019-0367] [PMID: 31916480]
[http://dx.doi.org/10.1016/S0924-977X(02)00098-6] [PMID: 12468012]
[http://dx.doi.org/10.1016/j.brainresbull.2022.09.017] [PMID: 36162603]
[http://dx.doi.org/10.1186/s13052-018-0563-0] [PMID: 30442184]
[http://dx.doi.org/10.1016/j.neuron.2013.12.023] [PMID: 24411725]
[http://dx.doi.org/10.2174/13816128113199990463] [PMID: 23789948]
[http://dx.doi.org/10.1038/jcbfm.2012.126] [PMID: 22929442]
[http://dx.doi.org/10.3390/pharmaceutics11100540] [PMID: 31627301]
[http://dx.doi.org/10.1172/JCI109433] [PMID: 447850]
[http://dx.doi.org/10.2174/138920011798357051] [PMID: 21568937]
[http://dx.doi.org/10.3390/pharmaceutics14050987] [PMID: 35631573]
[http://dx.doi.org/10.1186/s12987-020-00196-2] [PMID: 32375819]
[http://dx.doi.org/10.1016/B978-0-12-804279-3.00002-2] [PMID: 29110772]
[http://dx.doi.org/10.1016/j.addr.2019.11.009] [PMID: 31790711]
[http://dx.doi.org/10.2174/1567201043334542] [PMID: 16305398]
[http://dx.doi.org/10.1080/17425255.2018.1513493] [PMID: 30118608]
[http://dx.doi.org/10.3390/ijms17060806] [PMID: 27231900]
[http://dx.doi.org/10.1155/2021/6623031]
[http://dx.doi.org/10.1039/C5BM00383K] [PMID: 26646694]
[http://dx.doi.org/10.1016/j.jddst.2022.103932]
[http://dx.doi.org/10.1016/j.apsb.2016.04.001] [PMID: 27471676]
[http://dx.doi.org/10.2174/1570159X11311020006] [PMID: 23997754]
[http://dx.doi.org/10.1016/j.ajps.2022.05.002] [PMID: 36105313]
[http://dx.doi.org/10.1016/j.jconrel.2014.05.056] [PMID: 24943246]
[http://dx.doi.org/10.4110/in.2016.16.1.33] [PMID: 26937230]
[http://dx.doi.org/10.2174/0929866521666140807121903] [PMID: 25106905]
[http://dx.doi.org/10.1016/S1076-6332(03)80545-7] [PMID: 11345268]
[http://dx.doi.org/10.1080/02688690120036775] [PMID: 11360371]
[http://dx.doi.org/10.2147/IJN.S231479] [PMID: 32431498]
[http://dx.doi.org/10.1007/s00232-014-9637-0] [PMID: 24573305]
[http://dx.doi.org/10.1248/cpb.c19-00854] [PMID: 32238649]
[http://dx.doi.org/10.1146/annurev-pharmtox-010814-124852] [PMID: 25340933]
[http://dx.doi.org/10.1016/j.msec.2017.02.056] [PMID: 28482500]
[http://dx.doi.org/10.1517/17425240902806383] [PMID: 19327042]
[http://dx.doi.org/10.1007/s13346-022-01220-8] [PMID: 36245060]
[http://dx.doi.org/10.3390/molecules25081929] [PMID: 32326318]
[http://dx.doi.org/10.1517/17425247.2013.790887] [PMID: 23586809]
[http://dx.doi.org/10.1016/j.ejcb.2009.02.001] [PMID: 19324456]
[http://dx.doi.org/10.1517/17425247.2015.1069815] [PMID: 26289676]
[http://dx.doi.org/10.1016/j.brainresbull.2018.10.009] [PMID: 30449731]
[http://dx.doi.org/10.1016/j.ijpharm.2007.03.025] [PMID: 17475423]
[http://dx.doi.org/10.3390/pharmaceutics13122049] [PMID: 34959331]
[http://dx.doi.org/10.3390/pharmaceutics12030251] [PMID: 32168767]
[http://dx.doi.org/10.1016/j.apsb.2021.02.012] [PMID: 33996407]
[http://dx.doi.org/10.53879/id.54.09.10774]
[http://dx.doi.org/10.1016/j.jddst.2021.102533]
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.032] [PMID: 31095983]
[http://dx.doi.org/10.3390/pharmaceutics12121230] [PMID: 33352959]
[http://dx.doi.org/10.1016/j.reactfunctpolym.2019.104430]
[http://dx.doi.org/10.1016/j.eurpolymj.2020.109607]
[http://dx.doi.org/10.1016/j.cej.2018.03.176]
[http://dx.doi.org/10.1080/10717544.2020.1760960] [PMID: 32400219]
[http://dx.doi.org/10.1016/j.ejmech.2020.112905] [PMID: 33069435]
[http://dx.doi.org/10.1016/j.bioadv.2022.213118] [PMID: 36182834]
[http://dx.doi.org/10.1007/s11051-021-05175-8]
[PMID: 25749276]
[http://dx.doi.org/10.3109/10717544.2013.860501] [PMID: 24286183]
[http://dx.doi.org/10.3109/1061186X.2014.994097] [PMID: 25539073]
[http://dx.doi.org/10.3390/pharmaceutics10020040] [PMID: 29601486]
[http://dx.doi.org/10.17795/jjnpp-20126] [PMID: 25237648]
[http://dx.doi.org/10.1016/j.ejpb.2023.01.007] [PMID: 36642283]
[http://dx.doi.org/10.4103/0250-474X.56015] [PMID: 20490289]
[http://dx.doi.org/10.1016/j.ijpharm.2004.02.014] [PMID: 15113617]
[http://dx.doi.org/10.1016/S0378-5173(01)00825-0] [PMID: 11604255]
[http://dx.doi.org/10.1208/s12249-010-9413-0] [PMID: 20354916]
[http://dx.doi.org/10.1517/17425247.2012.665367] [PMID: 22432690]
[http://dx.doi.org/10.3109/10611860903508788] [PMID: 20055752]
[http://dx.doi.org/10.1186/s43094-020-00053-x]
[http://dx.doi.org/10.4103/JIOH.JIOH_257_20]
[http://dx.doi.org/10.4062/biomolther.2013.109] [PMID: 24753823]
[http://dx.doi.org/10.1016/j.jobcr.2021.02.001] [PMID: 33717865]
[http://dx.doi.org/10.1016/j.ijpharm.2017.09.073] [PMID: 28982548]
[http://dx.doi.org/10.1080/10837450.2019.1659314] [PMID: 31437077]
[http://dx.doi.org/10.1016/j.ejps.2009.02.022] [PMID: 19491020]
[http://dx.doi.org/10.1016/j.jddst.2018.11.023]
[http://dx.doi.org/10.1021/acsami.1c03422] [PMID: 33840187]
[http://dx.doi.org/10.1007/s13346-022-01172-z] [PMID: 35622235]
[http://dx.doi.org/10.1080/10717544.2016.1245369] [PMID: 28156169]
[http://dx.doi.org/10.2147/DDDT.S350886] [PMID: 35586185]
[http://dx.doi.org/10.1016/j.biomaterials.2004.06.013] [PMID: 15576186]
[http://dx.doi.org/10.1016/j.jconrel.2012.04.016] [PMID: 22543012]
[http://dx.doi.org/10.1016/j.ejpb.2004.03.003] [PMID: 15296966]
[http://dx.doi.org/10.1155/2021/1546798]
[http://dx.doi.org/10.2147/IJN.S265659] [PMID: 33380794]
[http://dx.doi.org/10.1016/j.ejps.2007.08.006] [PMID: 17920822]
[http://dx.doi.org/10.1016/j.ijpharm.2014.04.015] [PMID: 24709220]
[http://dx.doi.org/10.1080/1061186X.2017.1350858] [PMID: 28682134]
[http://dx.doi.org/10.1016/j.xphs.2018.04.007] [PMID: 29665379]
[http://dx.doi.org/10.1016/j.ejpb.2008.04.025] [PMID: 18644705]
[http://dx.doi.org/10.2174/1574885510999150505171515]
[http://dx.doi.org/10.1080/03639040801926030] [PMID: 18612913]
[http://dx.doi.org/10.1016/S0378-5173(03)00259-X] [PMID: 12818813]
[http://dx.doi.org/10.1021/bm0496965] [PMID: 15530052]
[http://dx.doi.org/10.1016/j.carbpol.2016.08.073] [PMID: 27702506]
[http://dx.doi.org/10.1016/j.ejps.2017.08.028] [PMID: 28843864]
[http://dx.doi.org/10.1016/j.jsps.2018.03.014] [PMID: 30202226]
[http://dx.doi.org/10.1016/j.jddst.2018.03.028]
[http://dx.doi.org/10.1016/j.carbpol.2016.08.068] [PMID: 27842839]
[http://dx.doi.org/10.1016/j.colsurfb.2016.03.028] [PMID: 26998870]
[http://dx.doi.org/10.1016/j.ijpharm.2012.03.054] [PMID: 22503953]
[http://dx.doi.org/10.1016/S0378-5173(03)00362-4] [PMID: 12954185]
[http://dx.doi.org/10.1016/j.ijpharm.2015.12.070] [PMID: 26748362]
[http://dx.doi.org/10.1016/j.biomaterials.2004.07.055] [PMID: 15603827]
[http://dx.doi.org/10.1016/j.ijpharm.2009.07.035] [PMID: 19666095]
[http://dx.doi.org/10.1002/jps.24693] [PMID: 26580704]
[http://dx.doi.org/10.1016/j.heliyon.2017.e00390] [PMID: 28920092]
[http://dx.doi.org/10.1007/s11095-006-9104-4] [PMID: 17096184]
[http://dx.doi.org/10.3390/md16100373] [PMID: 30304825]
[http://dx.doi.org/10.1080/17425247.2020.1731469] [PMID: 32067500]
[http://dx.doi.org/10.1295/polymj.35.804]
[http://dx.doi.org/10.1016/S0032-3861(02)00771-1]
[http://dx.doi.org/10.1016/j.ijpharm.2015.08.047] [PMID: 26302862]
[http://dx.doi.org/10.1208/s12249-011-9678-y] [PMID: 21879392]
[PMID: 22457595]
[http://dx.doi.org/10.2147/IJN.S213086] [PMID: 31413562]
[http://dx.doi.org/10.3389/fphar.2021.691936] [PMID: 34234679]
[http://dx.doi.org/10.1089/adt.2022.088] [PMID: 36576871]
[http://dx.doi.org/10.3390/pharmaceutics14071374] [PMID: 35890270]
[http://dx.doi.org/10.3390/pharmaceutics13050646] [PMID: 34062873]
[http://dx.doi.org/10.3390/nano9020147] [PMID: 30682799]
[http://dx.doi.org/10.2147/IJN.S247935] [PMID: 32440115]
[http://dx.doi.org/10.1049/iet-nbt.2019.0156] [PMID: 32433032]
[http://dx.doi.org/10.2147/IJN.S277352] [PMID: 33324051]
[http://dx.doi.org/10.3390/gels8060342] [PMID: 35735686]
[http://dx.doi.org/10.5530/ijper.47.3.6]
[PMID: 26770349]
[http://dx.doi.org/10.3390/pharmaceutics12060485] [PMID: 32471119]
[http://dx.doi.org/10.1016/j.jconrel.2015.12.044] [PMID: 26732557]
[http://dx.doi.org/10.2478/acph-2020-0032] [PMID: 32074067]
[http://dx.doi.org/10.2147/IJN.S258791] [PMID: 32801690]
[http://dx.doi.org/10.3390/pharmaceutics13111828] [PMID: 34834242]
[http://dx.doi.org/10.3390/pharmaceutics13081216] [PMID: 34452177]
[http://dx.doi.org/10.1016/j.ijpharm.2018.07.014] [PMID: 30033394]
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00938] [PMID: 30392378]
[http://dx.doi.org/10.3109/08982104.2014.954129] [PMID: 25203610]
[http://dx.doi.org/10.1016/j.xphs.2017.08.024] [PMID: 28923321]
[http://dx.doi.org/10.1016/j.ijpharm.2018.01.032] [PMID: 29366939]
[http://dx.doi.org/10.1016/j.jddst.2020.101778]
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