Abstract
Introduction: The goal of this study was to see if ascorbic acid grafted polylactic glycolic acid-b-polyethylene glycol nanoparticles (PLGA-b-PEG NPs) might boost the carrying or transport capacity of rivastigmine(RSM) to the brain via choroid plexus Sodium-dependent vitamin C transporter 2 (SVCT2 transporters). The IR and 1H NMR, were used to characterise the PLGA-b-PEG copolymer.
Methods: Nanoprecipitation method was used to make PLGA-b-PEG NPs. To promote SVCT2- mediated transportation of ascorbic acid (Asc) into the brain, PLGA-b-PEG NPs of acceptable size, polydispersity, and drug loading were bound with ascorbic acid (PLGA-b-PEG-Asc). When compared to PLGA-b-mPEG NPs, the surface functionalization of NPs with ascorbic acid dramatically improved the cellular uptake of NPs in SVCT2 expressing NIH/3T3 cells. Radial Arm Maze Test, and Acetylcholinesterase (AChE) activity in scopolamine-induced amnetic rats were used to assess in vivo pharmacodynamic effectiveness.
Results: In vivo pharmacodynamic tests revealed that drug loaded PLGA-b-PEG-Asc NPs had much greater therapeutic and sustained activity than free drugs, and PLGA-b-mPEG NPs to the brain.
Conclusion: As a consequence, the findings revealed that using ascorbic acid grafted PLGA-b-PEG NPs to deliver bioactives to the brain is a potential strategy.
Keywords: Ascorbic acid, Dementia, PEGylation, Rivastigmine, Targeted Drug Delivery System.
Graphical Abstract
[http://dx.doi.org/10.1186/s13024-019-0333-5] [PMID: 31375134]
[http://dx.doi.org/10.1016/j.biopsych.2014.05.006] [PMID: 24951455]
[http://dx.doi.org/10.1093/brain/awv316] [PMID: 26541346]
[http://dx.doi.org/10.2174/1871527313666140917095514] [PMID: 25230234]
[http://dx.doi.org/10.3389/fncel.2020.592607] [PMID: 33408613]
[http://dx.doi.org/10.1074/jbc.M111.321448] [PMID: 22505713]
[http://dx.doi.org/10.2174/1570159X13666150716165726] [PMID: 26813123]
[http://dx.doi.org/10.1074/jbc.M213153200] [PMID: 12637523]
[http://dx.doi.org/10.1073/pnas.0401667101] [PMID: 15173594]
[http://dx.doi.org/10.1016/S0166-2236(99)01543-X] [PMID: 10782126]
[http://dx.doi.org/10.2174/1570159X11311030006] [PMID: 24179466]
[http://dx.doi.org/10.2165/00002512-200421070-00004] [PMID: 15132713]
[http://dx.doi.org/10.3390/ijms15069809] [PMID: 24893223]
[http://dx.doi.org/10.1016/j.jconrel.2019.03.010] [PMID: 30876953]
[http://dx.doi.org/10.1186/s12951-021-00864-x] [PMID: 33926475]
[http://dx.doi.org/10.1016/j.ejps.2012.07.002] [PMID: 22796217]
[http://dx.doi.org/10.3389/fnins.2020.00494] [PMID: 32581676]
[http://dx.doi.org/10.4103/0250-474X.44589] [PMID: 20046766]
[http://dx.doi.org/10.3389/fnano.2020.589832]
[http://dx.doi.org/10.1038/s41565-020-0669-6] [PMID: 32251383]
[http://dx.doi.org/10.1016/j.biomaterials.2011.04.057] [PMID: 21616528]
[http://dx.doi.org/10.2174/157341308785161136]
[http://dx.doi.org/10.2147/IJN.S231480] [PMID: 32884267]
[http://dx.doi.org/10.1016/j.colsurfb.2019.110770] [PMID: 31926790]
[http://dx.doi.org/10.4172/jbb.1000224]
[http://dx.doi.org/10.3389/fnint.2020.00047] [PMID: 32973470]
[http://dx.doi.org/10.3389/fphys.2015.00397] [PMID: 26779027]
[http://dx.doi.org/10.1016/j.freeradbiomed.2008.12.018] [PMID: 19162177]
[http://dx.doi.org/10.1080/10717544.2018.1461955] [PMID: 30107760]
[http://dx.doi.org/10.1016/j.brainres.2008.01.039] [PMID: 18291351]
[http://dx.doi.org/10.1007/s00210-021-02096-0] [PMID: 34086100]
[http://dx.doi.org/10.1016/j.jconrel.2009.08.011] [PMID: 19699245]
[http://dx.doi.org/10.2174/2210681209666190228143636]
[http://dx.doi.org/10.1038/s41598-017-11611-4] [PMID: 28894228]
[http://dx.doi.org/10.1208/s12248-012-9444-4] [PMID: 23229335]
[http://dx.doi.org/10.1039/b702538f]
[http://dx.doi.org/10.1016/j.jep.2008.10.010] [PMID: 19007874]
[http://dx.doi.org/10.3109/1061186X.2012.719231] [PMID: 22994427]
[http://dx.doi.org/10.2478/v10007-008-0014-3] [PMID: 19103565]
[http://dx.doi.org/10.1097/WAD.0b013e318157205b] [PMID: 18525282]
[http://dx.doi.org/10.1016/j.ejpb.2010.07.007] [PMID: 20637869]
[http://dx.doi.org/10.1016/j.biomaterials.2010.04.009] [PMID: 20472283]
[http://dx.doi.org/10.1016/j.biomaterials.2006.12.016] [PMID: 17196249]
[http://dx.doi.org/10.5012/bkcs.2012.33.10.3225]
[http://dx.doi.org/10.1088/1748-6041/7/2/024107] [PMID: 22456931]
[http://dx.doi.org/10.1023/B:PHAM.0000036917.75634.be] [PMID: 15359578]
[http://dx.doi.org/10.1016/j.ejps.2004.09.011] [PMID: 15626579]
[http://dx.doi.org/10.3109/02652048.2013.834991] [PMID: 24124881]
[http://dx.doi.org/10.3797/scipharm.1211-20] [PMID: 24106679]
[http://dx.doi.org/10.1371/journal.pone.0087326] [PMID: 24489896]
[http://dx.doi.org/10.1208/pt0801014] [PMID: 17408214]
[http://dx.doi.org/10.1016/j.micromeso.2009.11.014]
[http://dx.doi.org/10.1016/j.ijpharm.2009.10.021] [PMID: 19840839]
[PMID: 24591829]
[http://dx.doi.org/10.1155/2018/1841937] [PMID: 29686925]
[http://dx.doi.org/10.4103/0253-7613.66841] [PMID: 20871769]
[http://dx.doi.org/10.1016/j.jgr.2013.11.003] [PMID: 24558303]