Liposomal Formulations of Anti-Alzheimer Drugs and siRNA for Nose-to-Brain Delivery: Design, Safety and Efficacy In Vitro.
Liposomes
Alzheimer Disease
/ drug therapy
Humans
Amyloid Precursor Protein Secretases
/ antagonists & inhibitors
Aspartic Acid Endopeptidases
/ antagonists & inhibitors
RNA, Small Interfering
/ administration & dosage
Administration, Intranasal
Donepezil
/ administration & dosage
Drug Delivery Systems
/ methods
Blood-Brain Barrier
/ metabolism
Brain
/ metabolism
Piperidines
/ administration & dosage
Nasal Mucosa
/ metabolism
Indans
/ administration & dosage
Amyloid beta-Peptides
/ metabolism
BACE-1 siRNA
alzheimer's disease
donepezil
liposomes
memantine
nose-to-brain delivery
Journal
The AAPS journal
ISSN: 1550-7416
Titre abrégé: AAPS J
Pays: United States
ID NLM: 101223209
Informations de publication
Date de publication:
04 Sep 2024
04 Sep 2024
Historique:
received:
11
07
2024
accepted:
15
08
2024
medline:
5
9
2024
pubmed:
5
9
2024
entrez:
4
9
2024
Statut:
epublish
Résumé
β-site amyloid precursor protein cleaving enzyme (BACE1) represents a key target for Alzheimer's disease (AD) therapy because it is essential for producing the toxic amyloid β (Aβ) peptide that plays a crucial role in the disease's development. BACE1 inhibitors are a promising approach to reducing Aβ levels in the brain and preventing AD progression. However, systemic delivery of such inhibitors to the brain demonstrates limited efficacy because of the presence of the blood-brain barrier (BBB). Nose-to-brain (NtB) delivery has the potential to overcome this obstacle. Liposomal drug delivery systems offer several advantages over traditional methods for delivering drugs and nucleic acids from the nose to the brain. The current study aims to prepare, characterize, and evaluate in vitro liposomal forms of donepezil, memantine, BACE-1 siRNA, and their combination for possible treatment of AD via NtB delivery. All the liposomal formulations were prepared using the rotary evaporation method. Their cellular internalization, cytotoxicity, and the suppression of beta-amyloid plaque and other pro-inflammatory cytokine expressions were studied. The Calu-3 Transwell model was used as an in vitro system for mimicking the anatomical and physiological conditions of the nasal epithelium and studying the suitability of the proposed formulations for possible NtB delivery. The investigation results show that liposomes provided the effective intracellular delivery of therapeutics, the potential to overcome tight junctions in BBB, reduced beta-amyloid plaque accumulation and pro-inflammatory cytokine expression, supporting the therapeutic potential of our approach.
Identifiants
pubmed: 39231845
doi: 10.1208/s12248-024-00967-x
pii: 10.1208/s12248-024-00967-x
doi:
Substances chimiques
Liposomes
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Aspartic Acid Endopeptidases
EC 3.4.23.-
RNA, Small Interfering
0
BACE1 protein, human
EC 3.4.23.46
Donepezil
8SSC91326P
Piperidines
0
Indans
0
Amyloid beta-Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
99Informations de copyright
© 2024. The Author(s).
Références
Neugroschl J, Wang S. Alzheimer’s disease: diagnosis and treatment across the spectrum of disease severity. Mt Sinai J Med. 2011;78(4):596–612. https://doi.org/10.1002/msj.20279 .
doi: 10.1002/msj.20279
pubmed: 21748748
pmcid: 3315348
Regelin AE, Fankhaenel S, Gurtesch L, Prinz C, von Kiedrowski G, Massing U. Biophysical and lipofection studies of DOTAP analogs. Biochim Biophys Acta. 2000;1464(1):151–64. https://doi.org/10.1016/s0005-2736(00)00126-7 .
doi: 10.1016/s0005-2736(00)00126-7
pubmed: 10704929
Bloom GS. Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA Neurol. 2014;71(4):505–8. https://doi.org/10.1001/jamaneurol.2013.5847 .
doi: 10.1001/jamaneurol.2013.5847
pubmed: 24493463
Dislich B, Lichtenthaler SF. The membrane-bound aspartyl protease BACE1: Molecular and Functional properties in Alzheimer’s Disease and Beyond. Front Physiol. 2012;3:8. https://doi.org/10.3389/fphys.2012.00008 .
doi: 10.3389/fphys.2012.00008
pubmed: 22363289
pmcid: 3281277
Peron R, Vatanabe IP, Manzine PR, Camins A, Cominetti MR. Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment. Pharmaceuticals (Basel). 2018;11(1). https://doi.org/10.3390/ph11010012 .
doi: 10.3390/ph11010012
pubmed: 29382156
Deuss M, Reiss K, Hartmann D. Part-time alpha-secretases: the functional biology of ADAM 9, 10 and 17. Curr Alzheimer Res. 2008;5(2):187–201. https://doi.org/10.2174/156720508783954686 .
doi: 10.2174/156720508783954686
pubmed: 18393804
Chasseigneaux S, Allinquant B. Functions of Aβ, sAPPα and sAPPβ: similarities and differences. J Neurochem. 2012;120(Suppl 1):99–108. https://doi.org/10.1111/j.1471-4159.2011.07584.x .
doi: 10.1111/j.1471-4159.2011.07584.x
pubmed: 22150401
Maia MA, Sousa E. BACE-1 and γ-Secretase as Therapeutic Targets for Alzheimer’s Disease. Pharmaceuticals (Basel). 2019;12(1). https://doi.org/10.3390/ph12010041 .
doi: 10.3390/ph12010041
pubmed: 30893882
Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease. Neuropharmacology. 2021;190:108352. https://doi.org/10.1016/j.neuropharm.2020.108352 .
doi: 10.1016/j.neuropharm.2020.108352
pubmed: 33035532
Hampel H, Mesulam MM, Cuello AC, Farlow MR, Giacobini E, Grossberg GT, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain. 2018;141(7):1917–33. https://doi.org/10.1093/brain/awy132 .
doi: 10.1093/brain/awy132
pubmed: 29850777
pmcid: 6022632
de Los Ríos C, Marco-Contelles J. Tacrines for Alzheimer’s disease therapy. III. The PyridoTacrines. Eur J Med Chem. 2019;166:381–9. https://doi.org/10.1016/j.ejmech.2019.02.005 .
doi: 10.1016/j.ejmech.2019.02.005
Cacabelos R. Donepezil in Alzheimer’s disease: from conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat. 2007;3(3):303–33.
pubmed: 19300564
pmcid: 2654795
Larkin HD. First Donepezil Transdermal Patch approved for Alzheimer Disease. JAMA. 2022;327(17):1642. https://doi.org/10.1001/jama.2022.6662 .
doi: 10.1001/jama.2022.6662
pubmed: 35503364
Wang R, Reddy PH. Role of glutamate and NMDA receptors in Alzheimer’s Disease. J Alzheimers Dis. 2017;57(4):1041–8. https://doi.org/10.3233/jad-160763 .
doi: 10.3233/jad-160763
pubmed: 27662322
pmcid: 5791143
Amiri A, Barreto G, Sathyapalan T, Sahebkar A. siRNA therapeutics: Future Promise for neurodegenerative diseases. Curr Neuropharmacol. 2021;19(11):1896–911. https://doi.org/10.2174/1570159x19666210402104054 .
doi: 10.2174/1570159x19666210402104054
pubmed: 33797386
pmcid: 9185778
Zhang W, Zhao H, Wu Q, Xu W, Xia M. Knockdown of BACE1-AS by siRNA improves memory and learning behaviors in Alzheimer’s disease animal model. Exp Ther Med. 2018;16(3):2080–6. https://doi.org/10.3892/etm.2018.6359 .
doi: 10.3892/etm.2018.6359
pubmed: 30186443
pmcid: 6122303
Lopez-Barbosa N, Garcia JG, Cifuentes J, Castro LM, Vargas F, Ostos C, et al. Multifunctional magnetite nanoparticles to enable delivery of siRNA for the potential treatment of Alzheimer’s. Drug Deliv. 2020;27(1):864–75. https://doi.org/10.1080/10717544.2020.1775724 .
doi: 10.1080/10717544.2020.1775724
pubmed: 32515999
pmcid: 8216449
Guo Q, Zheng X, Yang P, Pang X, Qian K, Wang P, et al. Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer׳s disease. Acta Pharm Sin B. 2019;9(3):590–603. https://doi.org/10.1016/j.apsb.2018.12.010 .
doi: 10.1016/j.apsb.2018.12.010
pubmed: 31193846
David S, Pitard B, Benoît JP, Passirani C. Non-viral nanosystems for systemic siRNA delivery. Pharmacol Res. 2010;62(2):100–14. https://doi.org/10.1016/j.phrs.2009.11.013 .
doi: 10.1016/j.phrs.2009.11.013
pubmed: 20006707
Engelhardt B, Sorokin L. The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol. 2009;31(4):497–511. https://doi.org/10.1007/s00281-009-0177-0 .
doi: 10.1007/s00281-009-0177-0
pubmed: 19779720
Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS. 2020;17(1):69. https://doi.org/10.1186/s12987-020-00230-3 .
doi: 10.1186/s12987-020-00230-3
pubmed: 33208141
pmcid: 7672931
Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC. The blood-brain barrier: an engineering perspective. Front Neuroeng. 2013;6:7. https://doi.org/10.3389/fneng.2013.00007 .
doi: 10.3389/fneng.2013.00007
pubmed: 24009582
pmcid: 3757302
Ohtsuki S, Terasaki T. Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm Res. 2007;24(9):1745–58. https://doi.org/10.1007/s11095-007-9374-5 .
doi: 10.1007/s11095-007-9374-5
pubmed: 17619998
Pulgar VM. Transcytosis to Cross the blood brain barrier, New advancements and challenges. Front Neurosci. 2018;12:1019. https://doi.org/10.3389/fnins.2018.01019 .
doi: 10.3389/fnins.2018.01019
pubmed: 30686985
Pires A, Fortuna A, Alves G, Falcão A. Intranasal drug delivery: how, why and what for? J Pharm Pharm Sci. 2009;12(3):288–311. https://doi.org/10.18433/j3nc79 .
doi: 10.18433/j3nc79
pubmed: 20067706
Sonvico F, Clementino A, Buttini F, Colombo G, Pescina S, Stanisçuaski Guterres S, et al. Surface-modified nanocarriers for nose-to-brain delivery: from Bioadhesion to Targeting. Pharmaceutics. 2018;10(1). https://doi.org/10.3390/pharmaceutics10010034 .
doi: 10.3390/pharmaceutics10010034
pubmed: 29543755
pmcid: 5874847
Tian L, Shang Y, Chen R, Bai R, Chen C, Inthavong K, et al. Correlation of regional deposition dosage for inhaled nanoparticles in human and rat olfactory. Part Fibre Toxicol. 2019;16(1):6. https://doi.org/10.1186/s12989-019-0290-8 .
doi: 10.1186/s12989-019-0290-8
pubmed: 30683122
pmcid: 6346518
Lee D, Minko T. Nanotherapeutics for nose-to-Brain Drug Delivery: an Approach to bypass the blood brain barrier. Pharmaceutics. 2021;13(12). https://doi.org/10.3390/pharmaceutics13122049 .
doi: 10.3390/pharmaceutics13122049
pubmed: 34959331
pmcid: 8704573
He Y, Zhang W, Xiao Q, Fan L, Huang D, Chen W, et al. Liposomes and liposome-like nanoparticles: from anti-fungal infection to the COVID-19 pandemic treatment. Asian J Pharm Sci. 2022. https://doi.org/10.1016/j.ajps.2022.11.002 .
doi: 10.1016/j.ajps.2022.11.002
pubmed: 36600898
pmcid: 9800940
Hong SS, Oh KT, Choi HG, Lim SJ. Liposomal formulations for nose-to-brain delivery: recent advances and future perspectives. Pharmaceutics. 2019;11(10). https://doi.org/10.3390/pharmaceutics11100540 .
doi: 10.3390/pharmaceutics11100540
pubmed: 31627301
pmcid: 6835450
Ivanova V, Garbuzenko OB, Reuhl KR, Reimer DC, Pozharov VP, Minko T. Inhalation treatment of pulmonary fibrosis by liposomal prostaglandin E2. Eur J Pharm Biopharm. 2013;84(2):335–44. https://doi.org/10.1016/j.ejpb.2012.11.023 .
doi: 10.1016/j.ejpb.2012.11.023
pubmed: 23228437
Skupin-Mrugalska P, Minko T. Development of liposomal vesicles for Osimertinib Delivery to EGFR mutation-positive Lung Cancer cells. Pharmaceutics. 2020;12(10). https://doi.org/10.3390/pharmaceutics12100939 .
doi: 10.3390/pharmaceutics12100939
pubmed: 33008019
pmcid: 7599969
Saad M, Garbuzenko OB, Minko T. Co-delivery of siRNA and an anticancer drug for treatment of multidrug-resistant cancer. Nanomed (Lond). 2008;3(6):761–76. https://doi.org/10.2217/17435889.3.6.761 .
doi: 10.2217/17435889.3.6.761
Baysal I, Ucar G, Gultekinoglu M, Ulubayram K, Yabanoglu-Ciftci S. Donepezil loaded PLGA-b-PEG nanoparticles: their ability to induce destabilization of amyloid fibrils and to cross blood brain barrier in vitro. J Neural Transm (Vienna). 2017;124(1):33–45. https://doi.org/10.1007/s00702-016-1527-4 .
doi: 10.1007/s00702-016-1527-4
pubmed: 26911385
Narola B, Singh AS, Santhakumar PR, Chandrashekhar TG. A Validated Stability-indicating reverse phase HPLC Assay Method for the determination of Memantine Hydrochloride Drug Substance with UV-Detection using Precolumn Derivatization technique. Anal Chem Insights. 2010;5:37–45. https://doi.org/10.4137/aci.s3936 .
doi: 10.4137/aci.s3936
pubmed: 20703320
pmcid: 2918351
Maeng H-J, Choi S-U, Jang D-J, Lee DW, Ahn B-N, Choi M-K, et al. Validation and application of a simple reverse phase HPLC method for in vitro dissolution studies of memantine hydrochloride tablet. J Pharm Invest. 2015;45(5):415–21. https://doi.org/10.1007/s40005-015-0184-1 .
doi: 10.1007/s40005-015-0184-1
Kontturi LS, van den Dikkenberg J, Urtti A, Hennink WE, Mastrobattista E. Light-triggered Cellular delivery of oligonucleotides. Pharmaceutics. 2019;11(2). https://doi.org/10.3390/pharmaceutics11020090 .
doi: 10.3390/pharmaceutics11020090
pubmed: 30795565
pmcid: 6410276
Xu X, Khan MA, Burgess DJ. A two-stage reverse dialysis in vitro dissolution testing method for passive targeted liposomes. Int J Pharm. 2012;426(1–2):211–8. https://doi.org/10.1016/j.ijpharm.2012.01.030 .
doi: 10.1016/j.ijpharm.2012.01.030
pubmed: 22301423
Sibinovska N, Žakelj S, Trontelj J, Kristan K. Applicability of RPMI 2650 and Calu-3 cell models for evaluation of nasal formulations. Pharmaceutics. 2022;14(2). https://doi.org/10.3390/pharmaceutics14020369 .
doi: 10.3390/pharmaceutics14020369
pubmed: 35214101
pmcid: 8877043
Zhang L, Du SY, Lu Y, Liu C, Tian ZH, Yang C, et al. Puerarin transport across a Calu-3 cell monolayer - an in vitro model of nasal mucosa permeability and the influence of paeoniflorin and menthol. Drug Des Devel Ther. 2016;10:2227–37. https://doi.org/10.2147/dddt.S110247 .
doi: 10.2147/dddt.S110247
pubmed: 27468226
pmcid: 4944921
Sousa F, Castro P. 3.4 - cell-based in vitro models for nasal permeability studies. In: Sarmento B, editor. Concepts and models for drug permeability studies. Woodhead Publishing; 2016. pp. 83–100.
doi: 10.1016/B978-0-08-100094-6.00006-7
Shipley MM, Mangold CA, Szpara ML. Differentiation of the SH-SY5Y human neuroblastoma cell line. J Vis Exp. 2016;108:53193. https://doi.org/10.3791/53193
Krishtal J, Bragina O, Metsla K, Palumaa P, Tõugu V. In situ fibrillizing amyloid-beta 1–42 induces neurite degeneration and apoptosis of differentiated SH-SY5Y cells. PLoS ONE. 2017;12(10):e0186636. https://doi.org/10.1371/journal.pone.0186636 .
doi: 10.1371/journal.pone.0186636
pubmed: 29065138
pmcid: 5655426
Sibinovska N, Žakelj S, Roškar R, Kristan K. Suitability and functional characterization of two Calu-3 cell models for prediction of drug permeability across the airway epithelial barrier. Int J Pharm. 2020;585:119484. https://doi.org/10.1016/j.ijpharm.2020.119484 .
doi: 10.1016/j.ijpharm.2020.119484
pubmed: 32485216
Shah V, Taratula O, Garbuzenko OB, Patil ML, Savla R, Zhang M, et al. Genotoxicity of different nanocarriers: possible modifications for the delivery of nucleic acids. Curr Drug Discov Technol. 2013;10(1):8–15.
pubmed: 22564170
pmcid: 3899095
Hong YJ, Han HJ, Youn YC, Park KW, Yang DW, Kim S, et al. Safety and tolerability of donepezil 23 mg with or without intermediate dose titration in patients with Alzheimer’s disease taking donepezil 10 mg: a multicenter, randomized, open-label, parallel-design, three-arm, prospective trial. Alzheimers Res Ther. 2019;11(1):37. https://doi.org/10.1186/s13195-019-0492-1 .
doi: 10.1186/s13195-019-0492-1
pubmed: 31039806
pmcid: 6492390
van Marum RJ. Update on the use of memantine in Alzheimer’s disease. Neuropsychiatr Dis Treat. 2009;5:237–47. https://doi.org/10.2147/ndt.s4048 .
doi: 10.2147/ndt.s4048
pubmed: 19557118
pmcid: 2695219
Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, Moradzadeh A, et al. Molecular mechanisms and Biological functions of siRNA. Int J Biomed Sci. 2017;13(2):48–57.
doi: 10.59566/IJBS.2017.13048
pubmed: 28824341
pmcid: 5542916
Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim Biophys Acta. 2007;1771(6):654–62. https://doi.org/10.1016/j.bbalip.2007.04.003 .
doi: 10.1016/j.bbalip.2007.04.003
pubmed: 17499021
pmcid: 2743068
Rajput A, Butani S. Donepezil HCl liposomes: development, characterization, cytotoxicity, and pharmacokinetic study. AAPS PharmSciTech. 2022;23(2):74. https://doi.org/10.1208/s12249-022-02209-9 .
doi: 10.1208/s12249-022-02209-9
pubmed: 35149912
Darvishi MH, Allahverdi A, Hashemzadeh H, Javadi HR. Investigation of the ionic conditions in SiRNA-mediated delivery through its carriers in the cell membrane: a molecular dynamic simulation. Sci Rep. 2022;12(1):17520. https://doi.org/10.1038/s41598-022-22509-1 .
doi: 10.1038/s41598-022-22509-1
pubmed: 36266467
pmcid: 9582388
Kedmi R, Ben-Arie N, Peer D. The systemic toxicity of positively charged lipid nanoparticles and the role of toll-like receptor 4 in immune activation. Biomaterials. 2010;31(26):6867–75. https://doi.org/10.1016/j.biomaterials.2010.05.027 .
doi: 10.1016/j.biomaterials.2010.05.027
pubmed: 20541799
Morrison EE, Costanzo RM. Morphology of olfactory epithelium in humans and other vertebrates. Microsc Res Tech. 1992;23(1):49–61. https://doi.org/10.1002/jemt.1070230105 .
doi: 10.1002/jemt.1070230105
pubmed: 1392071
Mistry A, Glud SZ, Kjems J, Randel J, Howard KA, Stolnik S, et al. Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium. J Drug Target. 2009;17(7):543–52. https://doi.org/10.1080/10611860903055470 .
doi: 10.1080/10611860903055470
pubmed: 19530905
Ahmad E, Feng Y, Qi J, Fan W, Ma Y, He H, et al. Evidence of nose-to-brain delivery of nanoemulsions: cargoes but not vehicles. Nanoscale. 2017;9(3):1174–83. https://doi.org/10.1039/c6nr07581a .
doi: 10.1039/c6nr07581a
pubmed: 28009915
Gabal YM, Kamel AO, Sammour OA, Elshafeey AH. Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route. Int J Pharm. 2014;473(1–2):442–57. https://doi.org/10.1016/j.ijpharm.2014.07.025 .
doi: 10.1016/j.ijpharm.2014.07.025
pubmed: 25062866
Moghimi SM, Simberg D. Pro-inflammatory concerns with lipid nanoparticles. Mol Ther. 2022;30(6):2109–10. https://doi.org/10.1016/j.ymthe.2022.04.011 .
doi: 10.1016/j.ymthe.2022.04.011
pubmed: 35487214
pmcid: 9047613
Sukhanova A, Bozrova S, Sokolov P, Berestovoy M, Karaulov A, Nabiev I. Dependence of nanoparticle toxicity on their physical and Chemical properties. Nanoscale Res Lett. 2018;13(1):44. https://doi.org/10.1186/s11671-018-2457-x .
doi: 10.1186/s11671-018-2457-x
pubmed: 29417375
pmcid: 5803171
Bonaccorso A, Musumeci T, Serapide MF, Pellitteri R, Uchegbu IF, Puglisi G. Nose to brain delivery in rats: Effect of surface charge of rhodamine B labeled nanocarriers on brain subregion localization. Colloids Surf B Biointerfaces. 2017;154:297–306. https://doi.org/10.1016/j.colsurfb.2017.03.035 .
doi: 10.1016/j.colsurfb.2017.03.035
pubmed: 28363190
Kanazawa T, Kaneko M, Niide T, Akiyama F, Kakizaki S, Ibaraki H, et al. Enhancement of nose-to-brain delivery of hydrophilic macromolecules with stearate- or polyethylene glycol-modified arginine-rich peptide. Int J Pharm. 2017;530(1–2):195–200. https://doi.org/10.1016/j.ijpharm.2017.07.077 .
doi: 10.1016/j.ijpharm.2017.07.077
pubmed: 28757255
London E, Brown DA. Insolubility of lipids in triton X-100: physical origin and relationship to sphingolipid/cholesterol membrane domains (rafts). Biochim Biophys Acta. 2000;1508(1–2):182–95. https://doi.org/10.1016/s0304-4157(00)00007-1 .
doi: 10.1016/s0304-4157(00)00007-1
pubmed: 11090825
Anderson M, Omri A. The effect of different lipid components on the in vitro stability and release kinetics of liposome formulations. Drug Deliv. 2004;11(1):33–9. https://doi.org/10.1080/10717540490265243 .
doi: 10.1080/10717540490265243
pubmed: 15168789
Silva S, Bicker J, Falcão A, Fortuna A. Air-liquid interface (ALI) impact on different respiratory cell cultures. Eur J Pharm Biopharm. 2023;184:62–82. https://doi.org/10.1016/j.ejpb.2023.01.013 .
doi: 10.1016/j.ejpb.2023.01.013
pubmed: 36696943
Kreft ME, Jerman UD, Lasič E, Hevir-Kene N, Rižner TL, Peternel L, et al. The characterization of the human cell line Calu-3 under different culture conditions and its use as an optimized in vitro model to investigate bronchial epithelial function. Eur J Pharm Sci. 2015;69:1–9. https://doi.org/10.1016/j.ejps.2014.12.017 .
doi: 10.1016/j.ejps.2014.12.017
pubmed: 25555374
Gänger S, Schindowski K. Tailoring formulations for intranasal nose-to-brain delivery: a Review on Architecture, Physico-Chemical characteristics and Mucociliary Clearance of the nasal olfactory mucosa. Pharmaceutics. 2018;10(3). https://doi.org/10.3390/pharmaceutics10030116 .
doi: 10.3390/pharmaceutics10030116
pubmed: 30081536
pmcid: 6161189
Jantas D, Pytel M, Mozrzymas JW, Leskiewicz M, Regulska M, Antkiewicz-Michaluk L, et al. The attenuating effect of memantine on staurosporine-, salsolinol- and doxorubicin-induced apoptosis in human neuroblastoma SH-SY5Y cells. Neurochem Int. 2008;52(4):864–77. https://doi.org/10.1016/j.neuint.2007.10.003 .
doi: 10.1016/j.neuint.2007.10.003
pubmed: 17996985
Chen B, Wang G, Li W, Liu W, Lin R, Tao J, et al. Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke. Exp Cell Res. 2017;351(2):163–72. https://doi.org/10.1016/j.yexcr.2016.12.028 .
doi: 10.1016/j.yexcr.2016.12.028
pubmed: 28069373
Shehata MK, Ismail AA, Kamel MA. Combined Donepezil with Astaxanthin via Nanostructured lipid carriers effective delivery to Brain for Alzheimer’s Disease in Rat Model. Int J Nanomed. 2023;18:4193–227. https://doi.org/10.2147/ijn.S417928 .
doi: 10.2147/ijn.S417928
Noh MY, Koh SH, Kim SM, Maurice T, Ku SK, Kim SH. Neuroprotective effects of donepezil against Aβ42-induced neuronal toxicity are mediated through not only enhancing PP2A activity but also regulating GSK-3β and nAChRs activity. J Neurochem. 2013;127(4):562–74. https://doi.org/10.1111/jnc.12319 .
doi: 10.1111/jnc.12319
pubmed: 23711227
Cutuli D, De Bartolo P, Caporali P, Tartaglione AM, Oddi D, D’Amato FR, et al. Neuroprotective effects of donepezil against cholinergic depletion. Alzheimers Res Ther. 2013;5(5):50. https://doi.org/10.1186/alzrt215 .
doi: 10.1186/alzrt215
pubmed: 24401551
pmcid: 3978431
Li Q, Chen M, Liu H, Yang L, Yang G. Expression of APP, BACE1, AChE and ChAT in an AD model in rats and the effect of donepezil hydrochloride treatment. Mol Med Rep. 2012;6(6):1450–4. https://doi.org/10.3892/mmr.2012.1102 .
doi: 10.3892/mmr.2012.1102
pubmed: 23023803
Mohamed LA, Qosa H, Kaddoumi A. Age-Related decline in brain and hepatic clearance of amyloid-Beta is rectified by the cholinesterase inhibitors Donepezil and Rivastigmine in rats. ACS Chem Neurosci. 2015;6(5):725–36. https://doi.org/10.1021/acschemneuro.5b00040 .
doi: 10.1021/acschemneuro.5b00040
pubmed: 25782004
Picón-Pagès P, Gutiérrez DA, Barranco-Almohalla A, Crepin G, Tajes M, Ill-Raga G, et al. Amyloid Beta-peptide increases BACE1 translation through the phosphorylation of the eukaryotic initiation Factor-2α. Oxid Med Cell Longev. 2020;2020:2739459. https://doi.org/10.1155/2020/2739459 .
doi: 10.1155/2020/2739459
pubmed: 33014268
pmcid: 7525306
Rani V, Verma R, Kumar K, Chawla R. Role of pro-inflammatory cytokines in Alzheimer’s disease and neuroprotective effects of pegylated self-assembled nanoscaffolds. Curr Res Pharmacol Drug Discov. 2023;4:100149. https://doi.org/10.1016/j.crphar.2022.100149 .
doi: 10.1016/j.crphar.2022.100149
pubmed: 36593925
Xie L, Lai Y, Lei F, Liu S, Liu R, Wang T. Exploring the association between interleukin-1β and its interacting proteins in Alzheimer’s disease. Mol Med Rep. 2015;11(5):3219–28. https://doi.org/10.3892/mmr.2015.3183 .
doi: 10.3892/mmr.2015.3183
pubmed: 25585621
pmcid: 4368090
Torres-Acosta N, O’Keefe JH, O’Keefe EL, Isaacson R, Small G. Therapeutic potential of TNF-α inhibition for Alzheimer’s Disease Prevention. J Alzheimers Dis. 2020;78(2):619–26. https://doi.org/10.3233/jad-200711 .
doi: 10.3233/jad-200711
pubmed: 33016914
pmcid: 7739965
Kummer KK, Zeidler M, Kalpachidou T, Kress M. Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine. 2021;144:155582. https://doi.org/10.1016/j.cyto.2021.155582 .
doi: 10.1016/j.cyto.2021.155582
pubmed: 34058569
Kim J, Lee HJ, Park SK, Park JH, Jeong HR, Lee S, et al. Donepezil regulates LPS and Aβ-Stimulated neuroinflammation through MAPK/NLRP3 Inflammasome/STAT3 signaling. Int J Mol Sci. 2021;22(19). https://doi.org/10.3390/ijms221910637 .
doi: 10.3390/ijms221910637
pubmed: 34638977
pmcid: 8508964
Kim HG, Moon M, Choi JG, Park G, Kim AJ, Hur J, et al. Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo. Neurotoxicology. 2014;40:23–32. https://doi.org/10.1016/j.neuro.2013.10.004 .
doi: 10.1016/j.neuro.2013.10.004
pubmed: 24189446
Wang Z, He X, Fan X. Postnatal administration of memantine rescues TNF-α-induced decreased hippocampal precursor proliferation. Neurosci Lett. 2018;662:173–80. https://doi.org/10.1016/j.neulet.2017.10.022 .
doi: 10.1016/j.neulet.2017.10.022
pubmed: 29042205
Peters I, Igbavboa U, Schütt T, Haidari S, Hartig U, Rosello X, et al. The interaction of beta-amyloid protein with cellular membranes stimulates its own production. Biochim Biophys Acta. 2009;1788(5):964–72. https://doi.org/10.1016/j.bbamem.2009.01.012 .
doi: 10.1016/j.bbamem.2009.01.012
pubmed: 19366591
pmcid: 2674130
Zimmermann M, Gardoni F, Marcello E, Colciaghi F, Borroni B, Padovani A, et al. Acetylcholinesterase inhibitors increase ADAM10 activity by promoting its trafficking in neuroblastoma cell lines. J Neurochem. 2004;90(6):1489–99. https://doi.org/10.1111/j.1471-4159.2004.02680.x .
doi: 10.1111/j.1471-4159.2004.02680.x
pubmed: 15341532
Alley GM, Bailey JA, Chen D, Ray B, Puli LK, Tanila H, et al. Memantine lowers amyloid-beta peptide levels in neuronal cultures and in APP/PS1 transgenic mice. J Neurosci Res. 2010;88(1):143–54. https://doi.org/10.1002/jnr.22172 .
doi: 10.1002/jnr.22172
pubmed: 19642202
pmcid: 2783840
Takada-Takatori Y, Nakagawa S, Kimata R, Nao Y, Mizukawa Y, Urushidani T, et al. Donepezil modulates amyloid precursor protein endocytosis and reduction by up-regulation of SNX33 expression in primary cortical neurons. Sci Rep. 2019;9(1):11922. https://doi.org/10.1038/s41598-019-47462-4 .
doi: 10.1038/s41598-019-47462-4
pubmed: 31417133
pmcid: 6695423
Rahman MM, Lendel C. Extracellular protein components of amyloid plaques and their roles in Alzheimer’s disease pathology. Mol Neurodegeneration. 2021;16(1):59. https://doi.org/10.1186/s13024-021-00465-0 .
doi: 10.1186/s13024-021-00465-0
Corace G, Angeloni C, Malaguti M, Hrelia S, Stein PC, Brandl M, et al. Multifunctional liposomes for nasal delivery of the anti-alzheimer drug tacrine hydrochloride. J Liposome Res. 2014;24(4):323–35. https://doi.org/10.3109/08982104.2014.899369 .
doi: 10.3109/08982104.2014.899369
pubmed: 24807822
Zheng X, Shao X, Zhang C, Tan Y, Liu Q, Wan X, et al. Intranasal H102 peptide-loaded liposomes for Brain Delivery to treat Alzheimer’s Disease. Pharm Res. 2015;32(12):3837–49. https://doi.org/10.1007/s11095-015-1744-9 .
doi: 10.1007/s11095-015-1744-9
pubmed: 26113236
Rassu G, Soddu E, Posadino AM, Pintus G, Sarmento B, Giunchedi P, et al. Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer’s therapy. Colloids Surf B Biointerfaces. 2017;152:296–301. https://doi.org/10.1016/j.colsurfb.2017.01.031 .
doi: 10.1016/j.colsurfb.2017.01.031
pubmed: 28126681