Abstract
Nose-to-brain drug delivery system is becoming a desirable alternative approach to conventional drug delivery systems used for the treatment of various neurological disorders. Trigeminal and olfactory routes are implicated to deliver drugs from the nose-to-brain, which bypasses the blood-brain barrier and the first-pass metabolism. In this review, nanocarrier systems are evaluated, screened, and tested in order to evaluate its physiochemical features and configuration to enhance the bioavailability of drugs in the brain after intranasal intervention. The application of specific ligand, surface modifications, and use of permeation enhancers to increase brain targeting are discussed. Furthermore, we discuss the in vivo animal and in vitro cell line-based models, which are actively being employed to explore the nanomaterial-driven drug transport mechanisms via the intranasal route. These models can be used to study absorption, diffusion, permeation, and toxicological and pharmacokinetic profile of the active pharmaceutical ingredient. Our review provides evidence to conclude that the potential of nose-to-brain delivery and role of functionalization of nanomaterials enhance the drug efficacy in brain diseases. We also conclude that the biorecognitive surface modifiers have the ability to enhance and optimize the drug delivery to the brain, and we provided our insights and outlooks to address challenges and opportunities for nanosystems to speed up clinical translation.
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25 August 2022
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References
Abd-Elal RM et al (2016) Trans-nasal zolmitriptan novasomes: in-vitro preparation, optimization and in-vivo evaluation of brain targeting efficiency. Drug Deliv 23(9):3374–3386
Abdelrahman FE et al (2017) Response surface optimization, Ex vivo and In vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone. Int J Pharm 530(1-2):1–11
Aderibigbe BA, Naki T (2019) Chitosan-based nanocarriers for nose to brain delivery. Appl Sci 9(11):2219
Agrawal M et al (2018) Nose-to-brain drug delivery: an update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Control Release 281:139–177
Agrawal M et al (2020) Stimuli-responsive In situ gelling system for nose-to-brain drug delivery. J Control Release
Ahmad N et al (2018) Impact of ultrasonication techniques on the preparation of novel Amiloride-nanoemulsion used for intranasal delivery in the treatment of epilepsy, Artificial Cells, Nanomedicine, and Biotechnology. 46(supp 3):S192–S207
Alexander A et al (2019) Recent expansions of novel strategies towards the drug targeting into the brain. Int J Nanomedicine 14:5895
Anand U, Feridooni T, Agu RU (2012) Novel mucoadhesive polymers for nasal drug delivery. Recent Adv Novel Drug Carrier Syst:315–330
Azambuja J et al (2020) Nasal administration of cationic nanoemulsions as CD73-siRNA delivery system for glioblastoma treatment: a new therapeutical approach. Mol Neurobiol 57(2):635–649
Bahadur S, Pathak K (2012) Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opin Drug Deliv 9(1):19–31
Baranei M et al (2020) Anticancer effect of green tea extract (GTE)-loaded pH-responsive niosome coated with PEG against different cell lines. Mater Today Commun:101751
Barani M et al (2018) Lawsone-loaded Niosome and its antitumor activity in MCF-7 breast Cancer cell line: a Nano-herbal treatment for Cancer. DARU J Pharm Sci 26(1):11–17
Barani M et al (2019a) Evaluation of carum-loaded niosomes on breast cancer cells: physicochemical properties, in vitro cytotoxicity, flow cytometric, DNA fragmentation and cell migration assay. Sci Rep 9(1):1–10
Barani M et al (2019b) In silico and in vitro study of magnetic niosomes for gene delivery: the effect of ergosterol and cholesterol. Mater Sci Eng C 94:234–246
Barani M et al (2020a) A new formulation of hydrophobin-coated niosome as a drug carrier to cancer cells. Mater Sci Eng C:110975
Barani M et al (2020b) Nanotreatment and nanodiagnosis of prostate cancer: recent updates. Nanomaterials 10(9):1696
Barani M et al (2020c) Comprehensive evaluation of gene expression in negative and positive trigger-based targeting niosomes in HEK-293 cell line. Iran J Pharm Res 19(1):166–180
Barani M et al (2020d) Nanotechnology in ovarian cancer: diagnosis and treatment. Life Sci:118,914
Barar J et al (2009) Ocular drug delivery; impact of in vitro cell culture models. J Ophthalmic Vis Res 4(4):238
de Barros T et al (2020) Cachexia: pathophysiology and ghrelin liposomes for nose-to-brain delivery. Int J Mol Sci 21(17):5974
Battaglia L et al (2018) Lipid nanoparticles for intranasal administration: application to nose-to-brain delivery. Expert Opin Drug Deliv 15(4):369–378
Betbeder D et al (2000) Biovector™ nanoparticles improve antinociceptive efficacy of nasal morphine. Pharm Res 17(6):743–748
Bilal M et al (2020) Nanomaterials for the treatment and diagnosis of Alzheimer's disease: an overview. NanoImpact:100,251
Bonferoni MC et al (2019) Nanoemulsions for “nose-to-brain” drug delivery. Pharmaceutics 11(2):84
Chalikwar SS et al (2013) Self-assembled, chitosan grafted PLGA nanoparticles for intranasal delivery: design, development and ex vivo characterization. Polym-Plast Technol Eng 52(4):368–380
Chen J et al (2012) Solanum tuberosum lectin-conjugated PLGA nanoparticles for nose-to-brain delivery: in vivo and in vitro evaluations. J Drug Target 20(2):174–184
Clementino A et al (2016) The nasal delivery of nanoencapsulated statins–an approach for brain delivery. Int J Nanomedicine 11:6575
Dae-Duk K (2007) Drug absorption studies: in situ, in vitro and in silico models. Springer, New York
Das SS et al (2020) Stimuli-responsive polymeric nanocarriers for drug delivery, imaging, and theragnosis. Polymers 12(6):1397
Davarpanah F et al (2018) Magnetic delivery of antitumor carboplatin by using PEGylated-Niosomes. DARU J Pharm Sci 26(1):57–64
Davarpanah AM et al (2019) (1-x) BaFe12O19/xCoFe2O4 hard/soft magnetic nanocomposites: Synthesis, physical characterization, and antibacterial activities study. J Mol Struct 1175:445–449
van Den Berg MP et al (2002) Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity. J Neurosci Methods 116(1):99–107
Devkar TB, Tekade AR, Khandelwal KR (2014) Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer. Colloids Surf B Biointerfaces 122:143–150
Dhakar RC et al (2011) A review on factors affecting the design of nasal drug delivery system. Int J Drug Deliv 3(2):194
Di Gioia S et al (2015) Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-β-cyclodextrin based nanoparticles. Eur J Pharm Biopharm 94:180–193
Ebrahimi AK, Barani M, Sheikhshoaie I (2018) Fabrication of a new superparamagnetic metal-organic framework with core-shell nanocomposite structures: characterization, biocompatibility, and drug release study. Mater Sci Eng C 92:349–355
Feng Y et al (2018) An update on the role of nanovehicles in nose-to-brain drug delivery. Drug Discov Today 23(5):1079–1088
Fonseca FN et al (2015) Mucoadhesive amphiphilic methacrylic copolymer-functionalized poly (ε-caprolactone) nanocapsules for nose-to-brain delivery of olanzapine. J Biomed Nanotechnol 11(8):1472–1481
Gabal YM et al (2014) Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route. Int J Pharm 473(1-2):442–457
Gänger S, Schindowski K (2018) Tailoring formulations for intranasal nose-to-brain delivery: a review on architecture, physico-chemical characteristics and mucociliary clearance of the nasal olfactory mucosa. Pharmaceutics 10(3):116
Gao X et al (2006) Lectin-conjugated PEG–PLA nanoparticles: preparation and brain delivery after intranasal administration. Biomaterials 27(18):3482–3490
Gao X et al (2007a) UEA I-bearing nanoparticles for brain delivery following intranasal administration. Int J Pharm 340(1-2):207–215
Gao X et al (2007b) Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release 121(3):156–167
Gao X et al (2008) Quantum dots for tracking cellular transport of lectin-functionalized nanoparticles. Biochem Biophys Res Commun 377(1):35–40
Gao M et al (2011) Synthesis and characterization of superparamagnetic Fe3O4@ SiO2 core-shell composite nanoparticles. World Jf Condensed Matter Phys 1(2):49–54
Gartziandia O et al (2015) Chitosan coated nanostructured lipid carriers for brain delivery of proteins by intranasal administration. Colloids Surf B Biointerfaces 134:304–313
Gartziandia O et al (2016) Intranasal administration of chitosan-coated nanostructured lipid carriers loaded with GDNF improves behavioral and histological recovery in a partial lesion model of Parkinson’s disease. J Biomed Nanotechnol 12(12):2220–2280
Ghazy E et al (2020a) Scrutinizing the therapeutic and diagnostic potential of nanotechnology in thyroid cancer: edifying drug targeting by nano-oncotherapeutics. J Drug Delivery Sci Technol:102,221
Ghazy E et al (2020b) Nanomaterials for Parkinson disease: recent progress. J Mol Struct:129,698
Ghosh S et al (2019) Surface engineered liposomal delivery of therapeutics across the blood brain barrier: recent advances, challenges and opportunities. Expert Opin Drug Deliv 16(12):1287–1311
Grossen P et al (2017) PEG-PCL-based nanomedicines: a biodegradable drug delivery system and its application. J Control Release 260:46–60
Guo J et al (2011) Aptamer-functionalized PEG–PLGA nanoparticles for enhanced anti-glioma drug delivery. Biomaterials 32(31):8010–8020
Guo Y et al (2013) The applications of Vitamin E TPGS in drug delivery. Eur J Pharm Sci 49(2):175–186
Gupta A (2020) Emerging applications of lectins in cancer detection and biomedicine. Mater Today: Proc 31:651–661
Hajizadeh MR et al (2019a) In vitro cytotoxicity assay of D-limonene niosomes: an efficient nano-carrier for enhancing solubility of plant-extracted agents. Res Pharm Sci 14(5):448
Hajizadeh MR et al (2019b) Diosgenin-loaded niosome as an effective phytochemical nanocarrier: physicochemical characterization, loading efficiency, and cytotoxicity assay. DARU J Pharm Sci 27(1):329–339
Hernando S et al (2018) Intranasal administration of TAT-conjugated lipid nanocarriers loading GDNF for Parkinson’s disease. Mol Neurobiol 55(1):145–155
Hornof M, Toropainen E, Urtti A (2005) Cell culture models of the ocular barriers. Eur J Pharm Biopharm 60(2):207–225
Huckaby JT, Lai SK (2018) PEGylation for enhancing nanoparticle diffusion in mucus. Adv Drug Deliv Rev 124:125–139
Illum L (2007) Nanoparticulate systems for nasal delivery of drugs: a real improvement over simple systems? J Pharm Sci 96(3):473–483
Jadhav KR et al (2007) Nasal drug delivery system-factors affecting and applications. Curr Drug Ther 2(1):27–38
Kamei N et al (2016) Visualization and quantitative assessment of the brain distribution of insulin through nose-to-brain delivery based on the cell-penetrating peptide noncovalent strategy. Mol Pharm 13(3):1004–1011
Kanazawa T (2015) Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles. Med Devices (Auckland, NZ) 8:57
Kanazawa T et al (2011) Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration. Pharm Res 28(9):2130–2139
Kanazawa T et al (2012) Suppression of tumor growth by systemic delivery of anti-VEGF siRNA with cell-penetrating peptide-modified MPEG–PCL nanomicelles. Eur J Pharm Biopharm 81(3):470–477
Kanazawa T et al (2013) Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles. Biomaterials 34(36):9220–9226
Kanazawa T et al (2017) Enhancement of nose-to-brain delivery of hydrophilic macromolecules with stearate-or polyethylene glycol-modified arginine-rich peptide. Int J Pharm 530(1-2):195–200
Kanazawa T et al (2019) Therapeutic effects in a transient middle cerebral artery occlusion rat model by nose-to-brain delivery of anti-TNF-alpha siRNA with cell-penetrating peptide-modified polymer micelles. Pharmaceutics 11(9):478
Kulkarni AD et al (2015) Nanotechnology-mediated nose to brain drug delivery for Parkinson’s disease: a mini review. J Drug Target 23(9):775–788
Li Y-P et al (2001) PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats. J Control Release 71(2):203–211
Li J et al (2011) Targeting the brain with PEG–PLGA nanoparticles modified with phage-displayed peptides. Biomaterials 32(21):4943–4950
Lin T et al (2016) Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides. Acta Pharm Sin B 6(4):352–358
Liu Z et al (2013) Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration. Biomaterials 34(15):3870–3881
Lu C-T et al (2015) Gelatin nanoparticle-mediated intranasal delivery of substance P protects against 6-hydroxydopamine-induced apoptosis: an in vitro and in vivo study. Drug Des Devel Ther 9:1955
Martins PP, Smyth HD, Cui Z (2019) Strategies to facilitate or block nose-to-brain drug delivery. Int J Pharm 570:118635
Mathieu V (2019) Development and characterization of formulations for the nose-to-brain delivery of ghrelin and the management of cachexia. Université de Mons.
Md S et al (2018) Nano-carrier enabled drug delivery systems for nose to brain targeting for the treatment of neurodegenerative disorders. J Drug Delivery Sci Technol 43:295–310
Mena-Hernández J et al (2020) Preparation and evaluation of mebendazole microemulsion for intranasal delivery: an alternative approach for glioblastoma treatment. AAPS PharmSciTech 21(7):1–12
Meng Q et al (2018) Intranasal delivery of Huperzine A to the brain using lactoferrin-conjugated N-trimethylated chitosan surface-modified PLGA nanoparticles for treatment of Alzheimer’s disease. Int J Nanomedicine 13:705
Merkus FW, van den Berg MP (2007) Can nasal drug delivery bypass the blood-brain barrier? Drugs in R & D 8(3):133–144
Migliore MM et al (2010) Brain delivery of proteins by the intranasal route of administration: a comparison of cationic liposomes versus aqueous solution formulations. J Pharm Sci 99(4):1745–1761
Misra A, Kher G (2012) Drug delivery systems from nose to brain. Curr Pharm Biotechnol 13(12):2355–2379
Mistry A, Stolnik S, Illum L (2009) Nanoparticles for direct nose-to-brain delivery of drugs. Int J Pharm 379(1):146–157
Mittal D et al (2014) Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv 21(2):75–86
Mukhtar M et al (2020) Nanomaterials for diagnosis and treatment of brain cancer: recent updates. Chemsensors 8(4):117
Muralidharan P et al (2014) Inhalable PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery as aerosolized colloidal dispersions and dry powder inhalers. Pharmaceutics 6(2):333–353
Musumeci T et al (2018) Tangential flow filtration technique: an overview on nanomedicine applications. Pharm Nanotechnol 6(1):48–60
Nehoff H et al (2014) Nanomedicine for drug targeting: strategies beyond the enhanced permeability and retention effect. Int J Nanomedicine 9:2539
Nikazar S et al (2020a) Revisiting the cytotoxicity of quantum dots: an in-depth overview. Biophys Rev:1–16
Nikazar S et al (2020b) Photo-and magnetothermally responsive nanomaterials for therapy, controlled drug delivery and imaging applications. ChemistrySelect 5(40):12,590–12,609
Okada H (2014) Targeted siRNA therapy using cytoplasm-responsive nanocarriers and cell-penetrating peptides. J Pharm Investig 44(7):505–516
Ong W-Y, Shalini S-M, Costantino L (2014) Nose-to-brain drug delivery by nanoparticles in the treatment of neurological disorders. Curr Med Chem 21(37):4247–4256
Pardeshi CV, Belgamwar VS (2013) Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood–brain barrier: an excellent platform for brain targeting. Expert Opin Drug Deliv 10(7):957–972
Pardeshi CV, Belgamwar VS (2018) N, N, N-trimethyl chitosan modified flaxseed oil based mucoadhesive neuronanoemulsions for direct nose to brain drug delivery. Int J Biol Macromol 120:2560–2571
Patel S et al (2011) Brain targeting of risperidone-loaded solid lipid nanoparticles by intranasal route. J Drug Target 19(6):468–474
Piazza J et al (2014) Haloperidol-loaded intranasally administered lectin functionalized poly (ethylene glycol)–block-poly (D, L)-lactic-co-glycolic acid (PEG–PLGA) nanoparticles for the treatment of schizophrenia. Eur J Pharm Biopharm 87(1):30–39
Piazzini V et al (2019) Chitosan coated human serum albumin nanoparticles: a promising strategy for nose-to-brain drug delivery. Int J Biol Macromol 129:267–280
Pillai AM et al (2020) Green synthesis and characterization of zinc oxide nanoparticles with antibacterial and antifungal activity. J Mol Struct:128,107
Quintana DS et al (2016) The promise and pitfalls of intranasally administering psychopharmacological agents for the treatment of psychiatric disorders. Mol Psychiatry 21(1):29–38
Rahdar A et al (2019a) Effect of tocopherol on the properties of Pluronic F127 microemulsions: physico-chemical characterization and in vivo toxicity. J Mol Liq 277:624–630
Rahdar A et al (2019b) Synthesis and characterization of highly efficacious Fe-doped ceria nanoparticles for cytotoxic and antifungal activity. Ceram Int 45(6):7950–7955
Rahdar A et al (2020a) The synthesis of methotrexate-loaded F127 microemulsions and their in vivo toxicity in a rat model. J Mol Liq:113449
Rahdar A et al (2020b) Synthesis, characterization, and intraperitoneal biochemical studies of zinc oxide nanoparticles in Rattus norvegicus. Appl Phys A 126:1–9
Rahdar A et al (2020c) Behavioral effects of zinc oxide nanoparticles on the brain of rats. Inorg Chem Commun 119:108,131
Rahdar A et al (2020d) Copolymer/graphene oxide nanocomposites as potential anticancer agents. Polymer Bull:1–22
Rahdar A et al (2020e) Gum-based cerium oxide nanoparticles for antimicrobial assay. Appl Phys A 126:1–9
Rahdar A et al (2020f) Deferasirox-loaded pluronic nanomicelles: synthesis, characterization, in vitro and in vivo studies. J Mol Liq:114,605
Rassu G et al (2017) Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer’s therapy. Colloids Surf B Biointerfaces 152:296–301
Sabir F, Ismail R, Csoka I (2020) Nose-to-brain delivery of antiglioblastoma drugs embedded into lipid nanocarrier systems: status quo and outlook. Drug Discov Today 25(1):185–194
Salade L et al (2017) Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia. Int J Nanomedicine 12:8531
Salem LH et al (2020) Coated lipidic nanoparticles as a new strategy for enhancing nose-to-brain delivery of a hydrophilic drug molecule. J Pharm Sci
Samaridou E, Alonso MJ (2018) Nose-to-brain peptide delivery–the potential of nanotechnology. Bioorg Med Chem 26(10):2888–2905
Samaridou E et al (2020) Nose-to-brain delivery of enveloped RNA-cell permeating peptide nanocomplexes for the treatment of neurodegenerative diseases. Biomaterials 230:119657
Saravani R et al (2020) Newly crocin-coated magnetite nanoparticles induce apoptosis and decrease VEGF expression in breast carcinoma cells. J Drug Delivery Sci Technol 60:101,987
Sawant RR, Torchilin VP (2010) Multifunctionality of lipid-core micelles for drug delivery and tumour targeting. Mol Membr Biol 27(7):232–246
Sayadi K et al (2020) Atorvastatin-loaded SBA-16 nanostructures: synthesis, physical characterization, and biochemical alterations in hyperlipidemic rats. J Mol Struct 1202:127,296
Sekerdag E et al (2017) A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles. J Control Release 261:187–198
Shamarekh KS et al (2020) Development and evaluation of protamine-coated PLGA nanoparticles for nose-to-brain delivery of tacrine: in-vitro and in-vivo assessment. J Drug Delivery Sci Technol:101,724
Sivasankarapillai VS et al (2020a) Cancer theranostic applications of MXene nanomaterials: recent updates. Nano-Struct Nano-Objects 22:100,457
Sivasankarapillai VS et al (2020b) On facing the SARS-CoV-2 (COVID-19) with combination of nanomaterials and medicine: possible strategies and first challenges. Nanomaterials 10(5):852
Sivasankarapillai V et al Progress in natural polymer engineered biomaterials for transdermal drug delivery systems. Mater Today Chem 19:100,382
Sonvico F et al (2018) Surface-modified nanocarriers for nose-to-brain delivery: from bioadhesion to targeting. Pharmaceutics 10(1):34
Sosnik A, das Neves J, Sarmento B (2014) Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: a review. Prog Polym Sci 39(12):2030–2075
Sousa F, Castro P (2016) Cell-based in vitro models for nasal permeability studies. In: Concepts and models for drug permeability studies. Elsevier, pp 83–100
Stevens J et al (2009) A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs. Pharm Res 26(8):1911–1917
Stützle M et al (2015) Nose-to-brain delivery of insulin for Alzheimer’s disease. ADMET and DMPK 3(3):190–202
Tafaghodi M et al (2004) Evaluation of the clearance characteristics of various microspheres in the human nose by gamma-scintigraphy. Int J Pharm 280(1-2):125–135
Taimoory SM et al (2018) The synthesis and characterization of a magnetite nanoparticle with potent antibacterial activity and low mammalian toxicity. J Mol Liq 265:96–104
Taki H et al (2012) Intranasal delivery of camptothecin-loaded tat-modified nanomicells for treatment of intracranial brain tumors. Pharmaceuticals 5(10):1092–1102
Torkzadeh-Mahani M et al (2020) A combined theoretical and experimental study to improve the thermal stability of recombinant D-lactate dehydrogenase immobilized on a novel superparamagnetic Fe3O4NPs@ metal–organic framework. Appl Organomet Chem 34(5):e5581
Ugwoke MI et al (2005) Nasal mucoadhesive drug delivery: background, applications, trends and future perspectives. Adv Drug Deliv Rev 57(11):1640–1665
Ullah I et al (2020) Nose-to-brain delivery of cancer-targeting paclitaxel-loaded nanoparticles potentiates antitumor effects in malignant glioblastoma. Mol Pharm 17(4):1193–1204
Upadhyay S et al (2011) Intranasal drug delivery system-a glimpse to become maestro. J Appl Pharm Sci 1(03):34–44
Urtti A (2006) Challenges and obstacles of ocular pharmacokinetics and drug delivery. Adv Drug Deliv Rev 58(11):1131–1135
Van Den Berg MP et al (2003) Hydroxocobalamin uptake into the cerebrospinal fluid after nasal and intravenous delivery in rats and humans. J Drug Target 11(6):325–331
Van Den Berg MP et al (2004) Uptake of melatonin into the cerebrospinal fluid after nasal and intravenous delivery: studies in rats and comparison with a human study. Pharm Res 21(5):799–802
Wang X, Chi N, Tang X (2008) Preparation of estradiol chitosan nanoparticles for improving nasal absorption and brain targeting. Eur J Pharm Biopharm 70(3):735–740
Warnken ZN et al (2016) Formulation and device design to increase nose to brain drug delivery. J Drug Delivery Sci Technol 35:213–222
Wu H et al (2012) A novel small Odorranalectin-bearing cubosomes: preparation, brain delivery and pharmacodynamic study on amyloid-β25–35-treated rats following intranasal administration. Eur J Pharm Biopharm 80(2):368–378
Xia H et al (2011) Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration. Biomaterials 32(36):9888–9898
Yadav S et al (2015) Comparative biodistribution and pharmacokinetic analysis of cyclosporine-a in the brain upon intranasal or intravenous administration in an oil-in-water nanoemulsion formulation. Mol Pharm 12(5):1523–1533
Yang T et al (2004) Cyclodextrins in nasal delivery of low-molecular-weight heparins: in vivo and in vitro studies. Pharm Res 21(7):1127–1136
Yasir M, Sara UVS (2014) Solid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation. Acta Pharm Sin B 4(6):454–463
Ying, W., The nose may help the brain: intranasal drug delivery for treating neurological diseases. 2008.
Yokoyama M (2005) Drug targeting with nano-sized carrier systems. J Artif Organs 8(2):77–84
Zaki N et al (2006) Rapid-onset intranasal delivery of metoclopramide hydrochloride: Part I. Influence of formulation variables on drug absorption in anesthetized rats. Int J Pharm 327(1-2):89–96
Zhang C et al (2014) Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer’s disease. Int J Pharm 461(1-2):192–202
Zhao Y-Z et al (2014) Gelatin nanostructured lipid carriers-mediated intranasal delivery of basic fibroblast growth factor enhances functional recovery in hemiparkinsonian rats. Nanomed Nanotechnol Biol Med 10(4):755–764
Zhao Y-Z et al (2016) Intranasal delivery of bFGF with nanoliposomes enhances in vivo neuroprotection and neural injury recovery in a rodent stroke model. J Control Release 224:165–175
Zheng X et al (2015) Intranasal H102 peptide-loaded liposomes for brain delivery to treat Alzheimer’s disease. Pharm Res 32(12):3837–3849
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Sabir, F. et al. (2022). Functionalized Nanoparticles in Drug Delivery: Strategies to Enhance Direct Nose-to-Brain Drug Delivery via Integrated Nerve Pathways. In: Thakur, A., Thakur, P., Khurana, S.P. (eds) Synthesis and Applications of Nanoparticles. Springer, Singapore. https://doi.org/10.1007/978-981-16-6819-7_21
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