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Drug Delivery Letters

Editor-in-Chief

ISSN (Print): 2210-3031
ISSN (Online): 2210-304X

Research Article

In-vitro and In-silico Examinations on Baicalein-loaded Solid Lipid Nanoparticles for Neurodegeneration

Author(s): Mansi Varshney, Bhavna Kumar*, Poorvi Varshney, Diwya Kumar Lal and Neeraj Kumar Sethiya

Volume 14, Issue 2, 2024

Published on: 25 January, 2024

Page: [151 - 164] Pages: 14

DOI: 10.2174/0122103031263883231230085819

Price: $65

Abstract

Background: In the current scenario, most of the population affected by neurogenerative disorders like Alzheimer's, Parkinson's, Huntington's, etc., exist among the 10% population 65 years of age group. Neurodegenerative diseases are characterised as chronic and progressive disorders that occur due to the degeneration of neurons. Baicalein is a flavonoid glycoside derived from the roots of Scutellaria baicalensis. Earlier research suggested that it could be used to treat neurodegenerative illnesses. Baicalein, which was selected for the current study, was designed into a solid lipid nanoparticle (SLN) formulation. The SLNs have low permeability across BBB and are delivered by the non-invasive route, i.e., through nasal delivery. The In-silico docking studies were performed to examine and compare the binding affinity of Baicalein to already established drugs on the two most viable targets of Alzheimer's disease, i.e., Beta- secretase and Acetylcholinesterase.

Objectives: The current work is to formulate and evaluate the Baicalein-loaded SLN for neurodegenerative disorders via a non-invasive route.

Methods: Baicalein loaded SLN was developed by solvent emulsification diffusion method, and formulation is characterised by using different parameters such as particle size analysis, zeta potential, scanning electron microscope, transverse electron microscope, X-ray diffraction, Differential scanning calorimetric, Fourier transforms -infrared radiations, drug entrapment, in-vitro drug release and in-silico docking studies.

Results: The particle size of Baicalein-loaded SLN was 755.2 ± 0.48 nm, the Polydispersity index was 0.06, and the zeta potential was -32.5 ± 0.36 mV. The drug entrapment and loading efficiency of the optimised formulation were found to be 94% ± 0.653 and 18.2% ± 0.553, respectively. Optimised formulation shows 84.6% ± 0.3% of drug release within 30 minutes, which demonstrates the sustained release of the drug.

Conclusion: Baicalein-loaded SLN is formulated and evaluated for the treatment of neurodegenerative disorders. SLN is an approach to overcome the challenge of bypassing the BBB by administering the drug via an intranasal route. Hence, when analysed together with the results of Baicalein-loaded SLN and in-silico studies, it was correlated that Baicalein proved to have a targeted moiety for neurodegeneration.

Keywords: Alzheimer's, baicalein, in-silico studies, intranasal route, neurodegeneration, solid lipid nanoparticles.

Graphical Abstract
[1]
Teixeira, M.I.; Lopes, C.M.; Amaral, M.H.; Costa, P.C. Current insights on lipid nanocarrier-assisted drug delivery in the treatment of neurodegenerative diseases. Eur. J. Pharm. Biopharm., 2020, 149, 192-217.
[http://dx.doi.org/10.1016/j.ejpb.2020.01.005] [PMID: 31982574]
[2]
Kumar Thakur, A.; Kamboj, P.; Goswami, K.; Ahuja, K. Pathophysiology and management of alzheimer’s disease: An overview. J. Anal. Pharm. Res., 2018, 7(2)
[http://dx.doi.org/10.15406/japlr.2018.07.00230]
[3]
Glenner, G.G.; Wong, C.W. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun., 1984, 120(3), 885-890.
[http://dx.doi.org/10.1016/S0006-291X(84)80190-4] [PMID: 6375662]
[4]
Anand, R.; Gill, K.D.; Mahdi, A.A. Therapeutics of alzheimer’s disease: Past, present and future. Neuropharmacology, 2014, 76(Pt A), 27-50.
[http://dx.doi.org/10.1016/j.neuropharm.2013.07.004] [PMID: 23891641]
[5]
Kellogg, C.C.; Fuller, K.S. Goodman and Fuller’s Pathology E-Book: Implications for the Physical Therapist; Elsevier Health Sciences, 2020.
[6]
Ek, C.J.; Wong, A.; Liddelow, S.A.; Johansson, P.A.; Dziegielewska, K.M.; Saunders, N.R. Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat. Toxicol. Lett., 2010, 197(1), 51-59.
[http://dx.doi.org/10.1016/j.toxlet.2010.04.025] [PMID: 20466047]
[7]
Brightman, M.W. Ultrastructure of brain endothelium. Physiology and pharmacology of the blood-brain barrier., 1992, 1-22.
[8]
Löscher, W.; Potschka, H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx, 2005, 2(1), 86-98.
[http://dx.doi.org/10.1602/neurorx.2.1.86] [PMID: 15717060]
[9]
Leontiadou, H.; Mark, A.E.; Marrink, S.J. Ion transport across transmembrane pores. Biophys. J., 2007, 92(12), 4209-4215.
[http://dx.doi.org/10.1529/biophysj.106.101295] [PMID: 17384063]
[10]
Zhou, S.Y.; Piyapolrungroj, N.; Pao, L.; Li, C.; Liu, G.; Zimmermann, E.; Fleisher, D. Regulation of paracellular absorption of cimetidine and 5-aminosalicylate in rat intestine. Pharm. Res., 1999, 16(11), 1781-1785.
[http://dx.doi.org/10.1023/A:1018974519984] [PMID: 10571287]
[11]
Flanagan, S.D.; Takahashi, L.H.; Liu, X.; Benet, L.Z. Contributions of saturable active secretion, passive transcellular, and paracellular diffusion to the overall transport of furosemide across adenocarcinoma (Caco-2) cells. J. Pharm. Sci., 2002, 91(4), 1169-1177.
[http://dx.doi.org/10.1002/jps.10099] [PMID: 11948555]
[12]
Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci., 2006, 7(1), 41-53.
[http://dx.doi.org/10.1038/nrn1824] [PMID: 16371949]
[13]
Pardridge, W.M. Blood-brain barrier delivery. Drug Discov. Today, 2007, 12(1-2), 54-61.
[http://dx.doi.org/10.1016/j.drudis.2006.10.013] [PMID: 17198973]
[14]
Hawkins, B.T.; Egleton, R.D. Pathophysiology of the blood-brain barrier: Animal models and methods. Curr. Top. Dev. Biol., 2007, 80, 277-309.
[http://dx.doi.org/10.1016/S0070-2153(07)80007-X] [PMID: 17950377]
[15]
Ricci, M.; Blasi, P.; Giovagnoli, S.; Rossi, C. Delivering drugs to the central nervous system: A medicinal chemistry or a pharmaceutical technology issue? Curr. Med. Chem., 2006, 13(15), 1757-1775.
[http://dx.doi.org/10.2174/092986706777452461] [PMID: 16787219]
[16]
Blasi, P.; Giovagnoli, S.; Schoubben, A.; Ricci, M.; Rossi, C. Solid lipid nanoparticles for targeted brain drug delivery. Adv. Drug Deliv. Rev., 2007, 59(6), 454-477.
[http://dx.doi.org/10.1016/j.addr.2007.04.011] [PMID: 17570559]
[17]
Bickel, U.; Yoshikawa, T.; Pardridge, W.M. Delivery of peptides and proteins through the blood-brain barrier. Adv. Drug Deliv. Rev., 2001, 46(1-3), 247-279.
[http://dx.doi.org/10.1016/S0169-409X(00)00139-3] [PMID: 11259843]
[18]
Bhise, S.B.; Yadav, A.V.; Avachat, A.M.; Malayandi, R. Bioavailability of intranasal drug delivery system. Asian J. Pharm., 2008, 2(4), 201.
[http://dx.doi.org/10.4103/0973-8398.45032]
[19]
Varsha, A.; Om, B.; Kuldeep, R.; Bindiya, P.; Riddhi, P. Poles apart inimitability of brain targeted drug delivery system in middle of NDDS. Int. J. Drug Dev. Res., 2014, 6(4), 15-27.
[20]
Saunders, N.R.; Ek, C.J.; Habgood, M.D.; Dziegielewska, K.M. Barriers in the brain: A renaissance? Trends Neurosci., 2008, 31(6), 279-286.
[http://dx.doi.org/10.1016/j.tins.2008.03.003] [PMID: 18471905]
[21]
Nabeshima, S.; Reese, T.S.; Landis, D.M.D.; Brightman, M.W. Junctions in the meninges and marginal glia. J. Comp. Neurol., 1975, 164(2), 127-169.
[http://dx.doi.org/10.1002/cne.901640202] [PMID: 810497]
[22]
Vassar, R.; Kuhn, P.H.; Haass, C.; Kennedy, M.E.; Rajendran, L.; Wong, P.C.; Lichtenthaler, S.F. Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects. J. Neurochem., 2014, 130(1), 4-28.
[http://dx.doi.org/10.1111/jnc.12715] [PMID: 24646365]
[23]
Hampel, H.; Mesulam, M.M.; Cuello, A.C.; Farlow, M.R.; Giacobini, E.; Grossberg, G.T.; Khachaturian, A.S.; Vergallo, A.; Cavedo, E.; Snyder, P.J.; Khachaturian, Z.S. The cholinergic system in the pathophysiology and treatment of alzheimer’s disease. Brain, 2018, 141(7), 1917-1933.
[http://dx.doi.org/10.1093/brain/awy132] [PMID: 29850777]
[24]
Xu, Y.; Cheng, S.; Sussman, J.; Silman, I.; Jiang, H. Computational studies on acetylcholinesterases. Molecules, 2017, 22(8), 1324.
[http://dx.doi.org/10.3390/molecules22081324] [PMID: 28796192]
[25]
a) Sussman, J.L.; Silman, I. Computational studies on cholinesterases: Strengthening our understanding of the integration of structure, dynamics and function. Neuropharmacology, 2020, 179, 108265.
[http://dx.doi.org/10.1016/j.neuropharm.2020.108265] [PMID: 32795461];
b) Craig, L.A.; Hong, N.S.; McDonald, R.J. Revisiting the cholinergic hypothesis in the development of alzheimer’s disease. Neurosci. Biobehav. Rev., 2011, 35(6), 1397-1409.
[http://dx.doi.org/10.1016/j.neubiorev.2011.03.001] [PMID: 21392524]
[26]
Islam, B.; Tabrez, S. Management of Alzheimer’s disease-An insight of the enzymatic and other novel potential targets. Int. J. Biol. Macromol., 2017, 97, 700-709.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.01.076] [PMID: 28111296]
[27]
Woodruff-Pak, D.S.; Lander, C.; Geerts, H. Nicotinic cholinergic modulation: Galantamine as a prototype. CNS Drug Rev., 2002, 8(4), 405-426.
[http://dx.doi.org/10.1111/j.1527-3458.2002.tb00237.x] [PMID: 12481195]
[28]
Zhou, L.; Tan, S.; Shan, Y.; Wang, Y.G.; Cai, W.; Huang, X.; Liao, X.; Li, H.; Zhang, L.; Zhang, B.; Lu, Z. Baicalein improves behavioral dysfunction induced by alzheimer’s disease in rats. Neuropsychiatr. Dis. Treat., 2016, 12, 3145-3152.
[http://dx.doi.org/10.2147/NDT.S117469] [PMID: 28003750]
[29]
Sahu, B.D.; Kumar, J.M.; Sistla, R. Baicalein, a bioflavonoid, prevents cisplatin-induced acute kidney injury by up-regulating antioxidant defenses and down-regulating the MAPKs and NF-κB pathways. PLoS One, 2015, 10(7), e0134139.
[http://dx.doi.org/10.1371/journal.pone.0134139] [PMID: 26222683]
[30]
Wang, Y.H.; Yu, H.T.; Pu, X.P.; Du, G.H. Baicalein prevents 6-hydroxydopamine-induced mitochondrial dysfunction in SH-SY5Y cells via inhibition of mitochondrial oxidation and up-regulation of DJ-1 protein expression. Molecules, 2013, 18(12), 14726-14738.
[http://dx.doi.org/10.3390/molecules181214726] [PMID: 24288000]
[31]
Patwardhan, R.S.; Sharma, D.; Thoh, M.; Checker, R.; Sandur, S.K. Baicalein exhibits anti-inflammatory effects via inhibition of NF-κB transactivation. Biochem. Pharmacol., 2016, 108, 75-89.
[http://dx.doi.org/10.1016/j.bcp.2016.03.013] [PMID: 27019135]
[32]
Goc, A.; Niedzwiecki, A.; Rath, M. In vitro evaluation of antibacterial activity of phytochemicals and micronutrients against Borrelia burgdorferi and Borrelia garinii. J. Appl. Microbiol., 2015, 119(6), 1561-1572.
[http://dx.doi.org/10.1111/jam.12970] [PMID: 26457476]
[33]
Han, Z.; Zhu, S.; Han, X.; Wang, Z.; Wu, S.; Zheng, R. Baicalein inhibits hepatocellular carcinoma cells through suppressing the expression of CD24. Int. Immunopharmacol., 2015, 29(2), 416-422.
[http://dx.doi.org/10.1016/j.intimp.2015.10.021] [PMID: 26548344]
[34]
Zhang, Z.; Cui, W.; Li, G.; Yuan, S.; Xu, D.; Hoi, M.P.M.; Lin, Z.; Dou, J.; Han, Y.; Lee, S.M.Y. Baicalein protects against 6-OHDA-induced neurotoxicity through activation of Keap1/Nrf2/HO-1 and involving PKCα and PI3K/AKT signaling pathways. J. Agric. Food Chem., 2012, 60(33), 8171-8182.
[http://dx.doi.org/10.1021/jf301511m] [PMID: 22838648]
[35]
Li, Y.; Zhao, J.; Hölscher, C. Therapeutic potential of baicalein in alzheimer’s disease and parkinson’s disease. CNS Drugs, 2017, 31(8), 639-652.
[http://dx.doi.org/10.1007/s40263-017-0451-y] [PMID: 28634902]
[36]
Li, C.; Lin, G.; Zuo, Z. Pharmacological effects and pharmacokinetics properties of radix scutellariae and its bioactive flavones. Biopharm. Drug Dispos., 2011, 32(8), 427-445.
[http://dx.doi.org/10.1002/bdd.771] [PMID: 21928297]
[37]
Gao, L.; Li, C.; Yang, R.Y.; Lian, W.W.; Fang, J.S.; Pang, X.C.; Qin, X.M.; Liu, A.L.; Du, G.H. Ameliorative effects of baicalein in MPTP-induced mouse model of parkinson’s disease: A microarray study. Pharmacol. Biochem. Behav., 2015, 133, 155-163.
[http://dx.doi.org/10.1016/j.pbb.2015.04.004] [PMID: 25895692]
[38]
Gu, X.H.; Xu, L.J.; Liu, Z.Q.; Wei, B.; Yang, Y.J.; Xu, G.G.; Yin, X.P.; Wang, W. The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of alzheimer’s disease. Behav. Brain Res., 2016, 311, 309-321.
[http://dx.doi.org/10.1016/j.bbr.2016.05.052] [PMID: 27233830]
[39]
Wei, D.; Tang, J.; Bai, W.; Wang, Y.; Zhang, Z. Ameliorative effects of baicalein on an amyloid-β induced Alzheimer’s disease rat model: A proteomics study. Curr. Alzheimer Res., 2014, 11(9), 869-881.
[PMID: 25274114]
[40]
Han, J.; Ji, Y.; Youn, K.; Lim, G.; Lee, J.; Kim, D.H.; Jun, M. Baicalein as a potential inhibitor against BACE1 and AChE: Mechanistic comprehension through in vitro and computational approaches. Nutrients, 2019, 11(11), 2694.
[http://dx.doi.org/10.3390/nu11112694] [PMID: 31703329]
[41]
Xie, Y.; Yang, W.; Chen, X.; Xiao, J. Inhibition of flavonoids on acetylcholine esterase: Binding and structure-activity relationship. Food Funct., 2014, 5(10), 2582-2589.
[http://dx.doi.org/10.1039/C4FO00287C] [PMID: 25143139]
[42]
Kumar, B.; Sharma, D. Recent patent advances for neurodegenerative disorders and its treatment. Recent Pat. Drug Deliv. Formul., 2018, 11(3), 158-172.
[http://dx.doi.org/10.2174/1872211311666171010123958] [PMID: 29032765]
[43]
Wilson, B. Therapeutic compliance of nanomedicine in alzheimer’s disease. Nanomedicine, 2011, 6(7), 1137-1139.
[http://dx.doi.org/10.2217/nnm.11.114] [PMID: 21929451]
[44]
Wilson, B.; Ambika, T.V.; Dharmesh Kumar Patel, R.; Jenita, J.L.; Priyadarshini, S.R.B. Nanoparticles based on albumin: Preparation, characterization and the use for 5-flurouracil delivery. Int. J. Biol. Macromol., 2012, 51(5), 874-878.
[http://dx.doi.org/10.1016/j.ijbiomac.2012.07.014] [PMID: 22820011]
[45]
Zeeshan, M.; Mukhtar, M.; Ain, Q.U.; Khan, S.; Ali, H. Nanopharmaceuticals: A boon to the brain-targeted drug delivery. In: Pharmaceutical Formulation Design-Recent Practices; IntechOpen, 2019; pp. 1-15.
[http://dx.doi.org/10.5772/intechopen.83040]
[46]
Wilson, B.; Lavanya, Y.; Priyadarshini, S.R.B.; Ramasamy, M.; Jenita, J.L. Albumin nanoparticles for the delivery of gabapentin: Preparation, characterization and pharmacodynamic studies. Int. J. Pharm., 2014, 473(1-2), 73-79.
[http://dx.doi.org/10.1016/j.ijpharm.2014.05.056] [PMID: 24999053]
[47]
Wilson, B.; Selvam, J.; Mukundan, G.K.; Premakumari, K.B.; Jenita, J.L. Albumin nanoparticles coated with polysorbate 80 for the targeted delivery of antiepileptic drug levetiracetam into the brain. Drug Deliv. Transl. Res., 2020, 10(6), 1853-1861.
[http://dx.doi.org/10.1007/s13346-020-00831-3] [PMID: 32783151]
[48]
Goldman, R. Intranasal drug delivery for children with acute illness. Curr. Drug Ther., 2006, 1(1), 127-130.
[http://dx.doi.org/10.2174/157488506775268470]
[49]
Jadhav, K.; Gambhire, M.; Shaikh, I.; Kadam, V.; Pisal, S. Nasal drug delivery system-factors affecting and applications. Curr. Drug Ther., 2007, 2(1), 27-38.
[http://dx.doi.org/10.2174/157488507779422374]
[50]
Illum, L. Nasal drug delivery—possibilities, problems and solutions. J. Control. Release, 2003, 87(1-3), 187-198.
[http://dx.doi.org/10.1016/S0168-3659(02)00363-2] [PMID: 12618035]
[51]
Talegaonkar, S.; Mishra, P.R. Intranasal delivery: An approach to bypass the blood brain barrier. Indian J. Pharmacol., 2004, 36(3), 140.
[52]
Joshi, A.S.; Patel, H.S.; Belgamwar, V.S.; Agrawal, A.; Tekade, A.R. Solid lipid nanoparticles of ondansetron HCl for intranasal delivery: development, optimization and evaluation. J. Mater. Sci. Mater. Med., 2012, 23(9), 2163-2175.
[http://dx.doi.org/10.1007/s10856-012-4702-7] [PMID: 22802103]
[53]
Bhavna, M.; Md, S.; Ali, M.; Ali, R.; Bhatnagar, A.; Baboota, S.; Ali, J. Donepezil nanosuspension intended for nose to brain targeting: In vitro and in vivo safety evaluation. Int. J. Biol. Macromol., 2014, 67, 418-425.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.03.022] [PMID: 24705169]
[54]
Kaur, I.P.; Bhandari, R.; Bhandari, S.; Kakkar, V. Potential of solid lipid nanoparticles in brain targeting. J. Control. Release, 2008, 127(2), 97-109.
[http://dx.doi.org/10.1016/j.jconrel.2007.12.018] [PMID: 18313785]
[55]
Gastaldi, L.; Battaglia, L.; Peira, E.; Chirio, D.; Muntoni, E.; Solazzi, I.; Gallarate, M.; Dosio, F. Solid lipid nanoparticles as vehicles of drugs to the brain: Current state of the art. Eur. J. Pharm. Biopharm., 2014, 87(3), 433-444.
[http://dx.doi.org/10.1016/j.ejpb.2014.05.004] [PMID: 24833004]
[56]
Graverini, G.; Piazzini, V.; Landucci, E.; Pantano, D.; Nardiello, P.; Casamenti, F.; Pellegrini-Giampietro, D.E.; Bilia, A.R.; Bergonzi, M.C. Solid lipid nanoparticles for delivery of andrographolide across the blood-brain barrier: In vitro and in vivo evaluation. Colloids Surf. B Biointerfaces, 2018, 161, 302-313.
[http://dx.doi.org/10.1016/j.colsurfb.2017.10.062] [PMID: 29096375]
[57]
Pardeshi, C.; Rajput, P.; Belgamwar, V.; Tekade, A.; Patil, G.; Chaudhary, K.; Sonje, A. Solid lipid based nanocarriers: An overview/Nanonosači na bazi čvrstih lipida: Pregled. Acta Pharm., 2012, 62(4), 433-472.
[http://dx.doi.org/10.2478/v10007-012-0040-z] [PMID: 23333884]
[58]
Mehnert, W.; Mäder, K. Solid lipid nanoparticles. Adv. Drug Deliv. Rev., 2012, 64, 83-101.
[http://dx.doi.org/10.1016/j.addr.2012.09.021] [PMID: 11311991]
[59]
Üner, M. Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): Their benefits as colloidal drug carrier systems. Pharmazie, 2006, 61(5), 375-386.
[60]
Trotta, M.; Debernardi, F.; Caputo, O. Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int. J. Pharm., 2003, 257(1-2), 153-160.
[http://dx.doi.org/10.1016/S0378-5173(03)00135-2] [PMID: 12711170]
[61]
Kipriye, Z.; Şenel, B.; Yenilmez, E. Preparation and evaluation of carvedilol-loaded solid lipid nanoparticles for targeted drug delivery. Trop. J. Pharm. Res., 2017, 16(9), 2057-2068.
[http://dx.doi.org/10.4314/tjpr.v16i9.4]
[62]
Lopes, C.E.; Langoski, G.; Klein, T.; Ferrari, P.C.; Farago, P.V. A simple HPLC method for the determination of Halcinonide in lipid nanoparticles: Development, validation, encapsulation efficiency, and in vitro drug permeation. Braz. J. Pharm. Sci., 2017, 53, 15250.
[63]
Sharma, D.; Maheshwari, D.; Philip, G.; Rana, R.; Bhatia, S.; Singh, M.; Gabrani, R.; Sharma, S.K.; Ali, J.; Sharma, R.K.; Dang, S. Formulation and optimization of polymeric nanoparticles for intranasal delivery of lorazepam using Box-Behnken design: In vitro and in vivo evaluation. BioMed Res. Int., 2014, 1-14.
[http://dx.doi.org/10.1155/2014/156010]
[64]
Silverstein, R.M.; Bassler, G.C. Spectrometric identification of organic compounds. J. Chem. Educ., 1962, 39(11), 546.
[http://dx.doi.org/10.1021/ed039p546]
[65]
Morsi, N.M.; Ghorab, D.M.; Badie, H.A. Brain targeted solid lipid nanoparticles for brain ischemia: preparation and in vitro characterization. Pharm. Dev. Technol., 2013, 18(3), 736-744.
[http://dx.doi.org/10.3109/10837450.2012.734513] [PMID: 23477526]
[66]
Gupta, S.; Chavhan, S.; Sawant, K.K. Self-nanoemulsifying drug delivery system for adefovir dipivoxil: Design, characterization, in vitro and ex vivo evaluation. Colloids Surf. A Physicochem. Eng. Asp., 2011, 392(1), 145-155.
[http://dx.doi.org/10.1016/j.colsurfa.2011.09.048]
[67]
Rose, P.W.; Prlić, A.; Altunkaya, A.; Bi, C.; Bradley, A.R.; Christie, C.H.; Costanzo, L.D.; Duarte, J.M.; Dutta, S.; Feng, Z.; Green, R.K. The RCSB protein data bank: Integrative view of protein, gene and 3D structural information. Nucleic Acids Res., 2016, gkw1000.
[68]
Wang, Y.; Xiao, J.; Suzek, T.O.; Zhang, J.; Wang, J.; Bryant, S.H. PubChem: A public information system for analyzing bioactivities of small molecules. Nucleic Acids Res., 2009, 37(Web Server), W623-W633.
[http://dx.doi.org/10.1093/nar/gkp456] [PMID: 19498078]
[69]
Das, B.; Yan, R. A close look at BACE1 inhibitors for alzheimer’s disease treatment. CNS Drugs, 2019, 33(3), 251-263.
[http://dx.doi.org/10.1007/s40263-019-00613-7] [PMID: 30830576]
[70]
Mygind, N.; Dahl, R. Anatomy, physiology and function of the nasal cavities in health and disease. Adv. Drug Deliv. Rev., 1998, 29(1-2), 3-12.
[http://dx.doi.org/10.1016/S0169-409X(97)00058-6] [PMID: 10837577]
[71]
Illum, L. Nasal drug delivery: New developments and strategies. Drug Discov. Today, 2002, 7(23), 1184-1189.
[http://dx.doi.org/10.1016/S1359-6446(02)02529-1] [PMID: 12547019]
[72]
Korsmeyer, R.W.; Gurny, R.; Doelker, E.; Buri, P.; Peppas, N.A. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm., 1983, 15(1), 25-35.
[http://dx.doi.org/10.1016/0378-5173(83)90064-9]
[73]
Hosny, K.; Banjar, Z.; Hariri, A.; Hassan, A.H. Solid lipid nanoparticles loaded with iron to overcome barriers for treatment of iron deficiency anemia. Drug Des. Devel. Ther., 2015, 9, 313-320.
[http://dx.doi.org/10.2147/DDDT.S77702] [PMID: 25609917]

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