{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:10:59Z","timestamp":1790892659434,"version":"4.1.0"},"reference-count":175,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNPq (Brazil)","award":["PVE 401196\/2014-3"],"award-info":[{"award-number":["PVE 401196\/2014-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer\u2019s disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality. While not disregarding the need for devices enabling a formulation deposition in the nose\u2019s upper part, surface modification of nanomedicines appears the key strategy to optimize drug delivery from the nasal cavity to the brain. In this review, nanomedicine delivery based on particle engineering exploiting surface electrostatic charges, mucoadhesive polymers, or chemical moieties targeting the nasal epithelium will be discussed and critically evaluated in relation to nose-to-brain delivery.<\/jats:p>","DOI":"10.3390\/pharmaceutics10010034","type":"journal-article","created":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T16:07:17Z","timestamp":1521130037000},"page":"34","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":243,"title":["Surface-Modified Nanocarriers for Nose-to-Brain Delivery: From Bioadhesion to Targeting"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7372-1456","authenticated-orcid":false,"given":"Fabio","family":"Sonvico","sequence":"first","affiliation":[{"name":"Interdipartmental Center for Innovation in Health Products, BIOPHARMANET TEC, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"},{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adryana","family":"Clementino","sequence":"additional","affiliation":[{"name":"Interdipartmental Center for Innovation in Health Products, BIOPHARMANET TEC, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"},{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-4823","authenticated-orcid":false,"given":"Francesca","family":"Buttini","sequence":"additional","affiliation":[{"name":"Interdipartmental Center for Innovation in Health Products, BIOPHARMANET TEC, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"},{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Colombo","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, Via Fossato di Mortara 17\/19, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pescina","sequence":"additional","affiliation":[{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Stanis\u00e7uaski Guterres","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil"},{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-1807","authenticated-orcid":false,"given":"Adriana","family":"Raffin Pohlmann","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, Brazil"},{"name":"Departamento de Qu\u00edmica Org\u00e2nica, Instituto de Qu\u00edmica, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6955-0957","authenticated-orcid":false,"given":"Sara","family":"Nicoli","sequence":"additional","affiliation":[{"name":"Interdipartmental Center for Innovation in Health Products, BIOPHARMANET TEC, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"},{"name":"Food and Drug Department, University of Parma, Parco Area delle Scienze 27\/a, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.3109\/03639045.2016.1160110","article-title":"Dry powder nasal drug delivery: Challenges, opportunities and a study of the commercial Teijin Puvlizer Rhinocort device and formulation","volume":"42","author":"Pozzoli","year":"2016","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.18433\/J3NC79","article-title":"Intranasal drug delivery: How, why and what for?","volume":"12","author":"Pires","year":"2009","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.addr.2011.11.010","article-title":"Modern methods for delivery of drugs across the blood-brain barrier","volume":"64","author":"Chen","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.nbd.2009.07.028","article-title":"Approaches to transport therapeutic drugs across the blood-brain barrier to treat brain diseases","volume":"37","author":"Gabathuler","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1007\/s00018-005-5094-3","article-title":"A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles","volume":"62","author":"Gil","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.ejps.2010.05.003","article-title":"Strategy for effective brain drug delivery","volume":"40","author":"Alam","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.addr.2011.10.007","article-title":"Nanotechnological advances for the delivery of CNS therapeutics","volume":"64","author":"Wong","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.drudis.2011.10.028","article-title":"Is there a clinical future for polymeric nanoparticles as brain-targeting drug delivery agents?","volume":"17","author":"Costantino","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1517\/17425247.2013.790887","article-title":"Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: An excellent platform for brain targeting","volume":"10","author":"Pardeshi","year":"2013","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.neuroscience.2004.05.029","article-title":"Delivery of insulin-like growth factor-I to the rat brain and spinal cord along olfactory and trigeminal pathways following intranasal administration","volume":"127","author":"Thorne","year":"2004","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1007\/s11095-012-0915-1","article-title":"Intranasal treatment of central nervous system dysfunction in humans","volume":"30","author":"Chapman","year":"2013","journal-title":"Pharm. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0928-0987(00)00087-7","article-title":"Transport of drugs from the nasal cavity to the central nervous system","volume":"11","author":"Illum","year":"2000","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2217\/14796708.3.1.1","article-title":"The nose may help the brain: Intranasal drug delivery for treating neurological diseases","volume":"3","author":"Ying","year":"2008","journal-title":"Future Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1002\/jps.21924","article-title":"Intranasal delivery to the central nervous system: Mechanisms and experimental considerations","volume":"99","author":"Dhuria","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Samaridou, E., and Alonso, M.J. (2018). Nose-to-brain peptide delivery\u2014The potential of nanotechnology. Bioorg. Med. Chem.","DOI":"10.1016\/j.bmc.2017.11.001"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"356","DOI":"10.2174\/1568026615666150108144655","article-title":"Opportunities and Challenges for the Nasal Administration of Nanoemulsions","volume":"15","author":"Comfort","year":"2015","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1517\/17425247.2015.1060959","article-title":"A novel intranasal breath-powered delivery system for sumatriptan: A review of technology and clinical application of the investigational product AVP-825 in the treatment of migraine","volume":"12","author":"Cady","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/10611860601029496","article-title":"Nose-to-brain delivery of TS-002, prostaglandin D2 analogue","volume":"15","author":"Yamada","year":"2007","journal-title":"J. Drug Target."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.antiviral.2011.09.012","article-title":"Brain distribution of ribavirin after intranasal administration","volume":"92","author":"Colombo","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.3390\/cancers5031020","article-title":"Formulations for intranasal delivery of pharmacological agents to combat brain disease: A new opportunity to tackle GBM?","volume":"5","author":"Wauthoz","year":"2013","journal-title":"Cancers"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s11060-013-1346-5","article-title":"A systematic review of inhaled intranasal therapy for central nervous system neoplasms: An emerging therapeutic option","volume":"116","author":"Peterson","year":"2014","journal-title":"J. Neurooncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jneuroim.2013.02.013","article-title":"Nasal administration of drugs as a new non-invasive strategy for efficient treatment of multiple sclerosis","volume":"258","author":"Duchi","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1080\/03639045.2016.1236808","article-title":"Pharmacodynamic and pharmacokinetic investigation of cyclodextrin-mediated asenapine maleate in situ nasal gel for improved bioavailability","volume":"43","author":"Kulkarni","year":"2017","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1517\/17425247.2015.1069815","article-title":"Intranasal gene delivery for treating Parkinsons disease: Overcoming the blood-brain barrier","volume":"12","author":"Aly","year":"2015","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3109\/1061186X.2013.876644","article-title":"Intranasal therapeutic strategies for management of Alzheimer\u2019s disease","volume":"22","author":"Sood","year":"2014","journal-title":"J. Drug Target."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jconrel.2017.03.029","article-title":"Intranasal delivery of N-terminal modified leptin-pluronic conjugate for treatment of obesity","volume":"263","author":"Yuan","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/S1359-6446(02)02452-2","article-title":"Permeability issues in nasal drug delivery","volume":"7","author":"Arora","year":"2002","journal-title":"Drug Discov. Today"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2165\/00126839-200708030-00001","article-title":"Can Nasal Drug Delivery Bypass the Blood-Brain Barrier?","volume":"8","author":"Merkus","year":"2007","journal-title":"Drugs R & D"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1211\/0022357022539","article-title":"Is nose-to-brain transport of drugs in man a reality?","volume":"56","author":"Illum","year":"2004","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1007\/s13346-012-0108-9","article-title":"Nasal drug delivery devices: Characteristics and performance in a clinical perspective\u2014A review","volume":"3","author":"Djupesland","year":"2012","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jconrel.2014.06.053","article-title":"Quantitative analysis of drug delivery to the brain via nasal route","volume":"189","author":"Kozlovskaya","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1208\/s12248-015-9724-x","article-title":"Emerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans","volume":"17","author":"Ruigrok","year":"2015","journal-title":"AAPS J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1212\/01.WNL.0000265401.62434.36","article-title":"Intranasal insulin improves cognition and modulates beta-amyloid in early AD","volume":"70","author":"Reger","year":"2008","journal-title":"Neurology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.3233\/JAD-161256","article-title":"Effects of Regular and Long-Acting Insulin on Cognition and Alzheimer\u2019s Disease Biomarkers: A Pilot Clinical Trial","volume":"57","author":"Craft","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e1136","DOI":"10.1038\/tp.2017.103","article-title":"Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: A randomized placebo-controlled double-blind crossover trial","volume":"7","author":"Quintana","year":"2017","journal-title":"Transl. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3389\/fnins.2013.00035","article-title":"Helping oxytocin deliver: Considerations in the development of oxytocin-based therapeutics for brain disorders","volume":"7","author":"Macdonald","year":"2013","journal-title":"Front. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1527-3458.2005.tb00053.x","article-title":"NAP: Research and development of a peptide derived from activity-dependent neuroprotective protein (ADNP)","volume":"11","author":"Gozes","year":"2005","journal-title":"CNS Drug Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1159\/000348347","article-title":"A double-blind, placebo-controlled, ascending-dose, randomized study to evaluate the safety, tolerability and effects on cognition of AL-108 after 12 weeks of intranasal administration in subjects with mild cognitive impairment","volume":"35","author":"Morimoto","year":"2013","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/S1474-4422(14)70088-2","article-title":"AL-108-231 Investigators Davunetide in patients with progressive supranuclear palsy: A randomised, double-blind, placebo-controlled phase 2\/3 trial","volume":"13","author":"Boxer","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4155\/tde.11.149","article-title":"Nasal-to-CNS drug delivery: Where are we now and where are we heading? An industrial perspective","volume":"3","author":"Landis","year":"2012","journal-title":"Ther. Deliv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.ejps.2013.03.012","article-title":"In vitro and in vivo characterization of meloxicam nanoparticles designed for nasal administration","volume":"50","author":"Bocsik","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2015.06.046","article-title":"Study of sodium hyaluronate-based intranasal formulations containing micro- or nanosized meloxicam particles","volume":"491","author":"Bartos","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ijpharm.2013.04.084","article-title":"Brain targeting of olanzapine via intranasal delivery of core\u2013shell difunctional block copolymer mixed nanomicellar carriers: In vitro characterization, ex vivo estimation of nasal toxicity and in vivo biodistribution studies","volume":"452","author":"Abdelbary","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1080\/10717544.2016.1223216","article-title":"Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: In vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies","volume":"23","author":"Nour","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"287","DOI":"10.2478\/v10007-008-0014-3","article-title":"A study of rivastigmine liposomes for delivery into the brain through intranasal route","volume":"58","author":"Arumugam","year":"2008","journal-title":"Acta Pharm."},{"key":"ref_46","first-page":"1","article-title":"Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability","volume":"2017","author":"Gupta","year":"2017","journal-title":"Biomed. Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.2147\/DDDT.S102500","article-title":"Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: Formulation, optimization and in vivo pharmacokinetics","volume":"11","author":"Fatouh","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1517\/17425247.2014.945416","article-title":"Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: In vitro characterization and in vivo efficacy in epilepsy","volume":"12","author":"Alam","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3773","DOI":"10.1021\/acs.molpharmaceut.6b00586","article-title":"Brain Targeting of Temozolomide via the Intranasal Route Using Lipid-Based Nanoparticles: Brain Pharmacokinetic and Scintigraphic Analyses","volume":"13","author":"Khan","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.nurt.2009.02.001","article-title":"Attenuation of Kindled Seizures by Intranasal Delivery of Neuropeptide-Loaded Nanoparticles","volume":"6","author":"Kubek","year":"2009","journal-title":"Neurotherapeutics"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1208\/s12249-015-0294-0","article-title":"Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles","volume":"16","author":"Sharma","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.3109\/10717544.2014.941076","article-title":"PNIPAM nanoparticles for targeted and enhanced nose-to-brain delivery of curcuminoids: UPLC\/ESI-Q-ToF-MS\/MS-based pharmacokinetics and pharmacodynamic evaluation in cerebral ischemia model","volume":"23","author":"Ahmad","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/jphp.12836","article-title":"Role of serum albumin as a nanoparticulate carrier for nose-to-brain delivery of R-flurbiprofen: Implications for the treatment of Alzheimer\u2019s disease","volume":"70","author":"Wong","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.toxlet.2014.04.020","article-title":"Effects of PAMAM dendrimers in the mouse brain after a single intranasal instillation","volume":"228","author":"Sone","year":"2014","journal-title":"Toxicol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.ijpharm.2016.09.042","article-title":"Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery","volume":"513","author":"Lungare","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3109\/10717544.2013.838014","article-title":"Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting","volume":"21","author":"Mahajan","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ijpharm.2009.06.019","article-title":"Nanoparticles for direct nose-to-brain delivery of drugs","volume":"379","author":"Mistry","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jconrel.2013.06.028","article-title":"Quantitative analysis of the brain-targeted delivery of drugs and model compounds using nano-delivery systems","volume":"171","author":"Kozlovskaya","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.3109\/03639045.2015.1052081","article-title":"Nanoneurotherapeutics approach intended for direct nose to brain delivery","volume":"41","author":"Md","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jconrel.2017.11.047","article-title":"Nanosystems in nose-to-brain drug delivery\u2014A review of non-clinical brain targeting studies","volume":"270","author":"Pires","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Feng, Y., He, H., Li, F., Lu, Y., Qi, J., and Wu, W. (2018). An update on the role of nanovehicles in nose-to-brain drug delivery. Drug Discov. Today.","DOI":"10.1016\/j.drudis.2018.01.005"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"775","DOI":"10.3109\/1061186X.2015.1020809","article-title":"Nanotechnology-mediated nose to brain drug delivery for Parkinson\u2019s disease: A mini review","volume":"23","author":"Kulkarni","year":"2015","journal-title":"J. Drug Target."},{"key":"ref_63","first-page":"4981","article-title":"Nanotechnology-based drug delivery systems for the treatment of Alzheimer\u2019s disease","volume":"10","author":"Chorilli","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.2174\/1381612821666150923095958","article-title":"Nose to Brain Delivery: New Trends in Amphiphile-Based \u201cSoft\u201d Nanocarriers","volume":"21","author":"Marianecci","year":"2015","journal-title":"Curr. Pharm. Des."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2147\/MDER.S70856","article-title":"Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles","volume":"8","author":"Kanazawa","year":"2015","journal-title":"Med. Devices"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21691401.2017.1420073","article-title":"Nose to brain transport pathways an overview: Potential of nanostructured lipid carriers in nose to brain targeting","volume":"7","author":"Selvaraj","year":"2017","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.ijpharm.2015.12.046","article-title":"Nanoparticle transport across in vitro olfactory cell monolayers","volume":"499","author":"Gartziandia","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jconrel.2014.07.045","article-title":"Nanoparticle penetration of human cervicovaginal mucus: The effect of polyvinyl alcohol","volume":"192","author":"Yang","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1002\/jps.23836","article-title":"Nose-to-brain delivery: Evaluation of polymeric nanoparticles on olfactory ensheathing cells uptake","volume":"103","author":"Musumeci","year":"2014","journal-title":"J. Pharm. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"4199","DOI":"10.1039\/C4NR06849A","article-title":"Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: In vitro studies on neural tissue cells","volume":"7","author":"Murali","year":"2015","journal-title":"Nanoscale"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1021\/acs.molpharmaceut.5b00088","article-title":"Nose-to-Brain Delivery: Investigation of the Transport of Nanoparticles with Different Surface Characteristics and Sizes in Excised Porcine Olfactory Epithelium","volume":"12","author":"Mistry","year":"2015","journal-title":"Mol. Pharm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1080\/10611860903055470","article-title":"Effect of physicochemical properties on intranasal nanoparticle transit into murine olfactory epithelium","volume":"17","author":"Mistry","year":"2009","journal-title":"J. Drug Target."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.addr.2008.11.002","article-title":"Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9217","DOI":"10.1021\/acsnano.5b03876","article-title":"Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex Vivo and Distribution in Vivo","volume":"9","author":"Xu","year":"2015","journal-title":"ACS Nano"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1039\/C6NR07581A","article-title":"Evidence of nose-to-brain delivery of nanoemulsions: Cargoes but not vehicles","volume":"9","author":"Ahmad","year":"2017","journal-title":"Nanoscale"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.ijpharm.2017.07.077","article-title":"Enhancement of nose-to-brain delivery of hydrophilic macromolecules with stearate- or polyethylene glycol-modified arginine-rich peptide","volume":"530","author":"Kanazawa","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.ijpharm.2014.07.025","article-title":"Effect of surface charge on the brain delivery of nanostructured lipid carriers in situ gels via the nasal route","volume":"473","author":"Gabal","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.jconrel.2014.05.003","article-title":"Chitosan in nasal delivery systems for therapeutic drugs","volume":"190","author":"Casettari","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.neuro.2011.12.001","article-title":"Neurological impacts from inhalation of pollutants and the nose-brain connection","volume":"33","author":"Lucchini","year":"2012","journal-title":"NeuroToxicology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jfda.2014.01.012","article-title":"Neurotoxicity of nanoscale materials","volume":"22","author":"Karmakar","year":"2014","journal-title":"J. Food Drug Anal."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1743-8977-7-42","article-title":"Risks from accidental exposures to engineered nanoparticles and neurological health effects: A critical review","volume":"7","author":"Mattsson","year":"2010","journal-title":"Part. Fibre Toxicol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0169-409X(97)00059-8","article-title":"Nasal mucociliary clearance as a factor in nasal drug delivery","volume":"29","author":"Marttin","year":"1998","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1016\/j.addr.2005.07.009","article-title":"Nasal mucoadhesive drug delivery: Background, applications, trends and future perspectives","volume":"57","author":"Ugwoke","year":"2005","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1016\/j.progpolymsci.2014.07.010","article-title":"Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: A review","volume":"39","author":"Sosnik","year":"2014","journal-title":"Prog. Polym. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ejps.2006.11.018","article-title":"Distribution and clearance of bioadhesive formulations from the olfactory region in man: Effect of polymer type and nasal delivery device","volume":"30","author":"Charlton","year":"2007","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ejpb.2008.10.009","article-title":"Sodium hyaluronate as a mucoadhesive component in nasal formulation enhances delivery of molecules to brain tissue","volume":"72","author":"Wolburg","year":"2009","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1023\/A:1007594602449","article-title":"Biovector nanoparticles improve antinociceptive efficacy of nasal morphine","volume":"17","author":"Betbeder","year":"2000","journal-title":"Pharm. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1166\/jbn.2015.2078","article-title":"Mucoadhesive amphiphilic methacrylic copolymer-functionalized poly(\u03b5-caprolactone) nanocapsules for nose-to-brain delivery of olanzapine","volume":"11","author":"Fonseca","year":"2014","journal-title":"J. Biomed. Nanotechnol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ejpb.2004.02.016","article-title":"Polysaccharide-decorated nanoparticles","volume":"58","author":"Lemarchand","year":"2004","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ejps.2011.10.002","article-title":"Albumin nanoparticles carrying cyclodextrins for nasal delivery of the anti-Alzheimer drug tacrine","volume":"44","author":"Luppi","year":"2011","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.colsurfb.2014.06.037","article-title":"Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer","volume":"122","author":"Devkar","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.carbpol.2012.02.051","article-title":"Venlafaxine loaded chitosan NPs for brain targeting: Pharmacokinetic and pharmacodynamic evaluation","volume":"89","author":"Haque","year":"2012","journal-title":"Carbohydr. Polym."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbamem.2008.09.016","article-title":"Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery","volume":"1788","author":"Deli","year":"2009","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ijpharm.2010.08.020","article-title":"Tight junction modulation by chitosan nanoparticles: Comparison with chitosan solution","volume":"400","author":"Vllasaliu","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijpharm.2006.02.055","article-title":"Evaluation of brain-targeting for the nasal delivery of estradiol by the microdialysis method","volume":"317","author":"Wang","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ejps.2012.04.013","article-title":"Development and evaluation of rivastigmine loaded chitosan nanoparticles for brain targeting","volume":"47","author":"Fazil","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5705","DOI":"10.2147\/IJN.S35329","article-title":"Development and evaluation of thymoquinone-encapsulated chitosan nanoparticles for nose-to-brain targeting: A pharmacoscintigraphic study","volume":"7","author":"Alam","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ejps.2012.12.007","article-title":"Bromocriptine loaded chitosan nanoparticles intended for direct nose to brain delivery: Pharmacodynamic, Pharmacokinetic and Scintigraphy study in mice model","volume":"48","author":"Md","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.3109\/03639045.2014.991400","article-title":"Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting","volume":"41","author":"Jafarieh","year":"2015","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"130","DOI":"10.3109\/10717544.2014.907372","article-title":"Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route","volume":"23","author":"Mittal","year":"2014","journal-title":"Drug Deliv."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.ijbiomac.2017.12.056","article-title":"Pramipexole dihydrochloride loaded chitosan nanoparticles for nose to brain delivery: Development, characterization and in vivo anti-Parkinson activity","volume":"109","author":"Raj","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1080\/02652048.2017.1375038","article-title":"Intranasal delivery of tapentadol hydrochloride\u2013loaded chitosan nanoparticles: Formulation, characterisation and its in vivo evaluation","volume":"34","author":"Javia","year":"2017","journal-title":"J. Microencapsul."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ijbiomac.2013.06.041","article-title":"Evaluation of neuropeptide loaded trimethyl chitosan nanoparticles for nose to brain delivery","volume":"61","author":"Kumar","year":"2013","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.ijpharm.2012.02.044","article-title":"Thiolated chitosan nanoparticles for the nasal administration of leuprolide: Bioavailability and pharmacokinetic characterization","volume":"428","author":"Shahnaz","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1002\/jps.22780","article-title":"Improved transnasal transport and brain uptake of tizanidine HCl-loaded thiolated chitosan nanoparticles for alleviation of pain","volume":"101","author":"Patel","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"759","DOI":"10.3109\/1061186X.2013.818676","article-title":"Intranasal delivery of cyclobenzaprine hydrochloride-loaded thiolated chitosan nanoparticles for pain relief","volume":"21","author":"Patel","year":"2013","journal-title":"J. Drug Target."},{"key":"ref_107","first-page":"865","article-title":"Pharmacological evaluation of nasal delivery of selegiline hydrochloride-loaded thiolated chitosan nanoparticles for the treatment of depression","volume":"44","author":"Singh","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.ejpb.2015.05.019","article-title":"Intranasal delivery of dopamine to the striatum using glycol chitosan\/sulfobutylether-\u03b2-cyclodextrin based nanoparticles","volume":"94","author":"Trapani","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1080\/03602559.2012.751999","article-title":"Self-Assembled, Chitosan Grafted PLGA Nanoparticles for Intranasal Delivery: Design, Development and Ex Vivo Characterization","volume":"52","author":"Chalikwar","year":"2013","journal-title":"Polym. Plast. Technol. Eng."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"8531","DOI":"10.2147\/IJN.S147650","article-title":"Development of coated liposomes loaded with ghrelin for nose-to-brain delivery for the treatment of cachexia","volume":"12","author":"Salade","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.2174\/1568026614666140329232252","article-title":"Expanding the Therapeutic Potential of Statins by Means of Nanotechnology Enabled Drug Delivery Systems","volume":"14","author":"Romana","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"625","DOI":"10.4155\/tde-2017-0044","article-title":"Drug delivery to the brain: How can nanoencapsulated statins be used in the clinic?","volume":"8","author":"Sonvico","year":"2017","journal-title":"Ther. Deliv."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"6575","DOI":"10.2147\/IJN.S119033","article-title":"The nasal delivery of nanoencapsulated statins\u2014An approach for brain delivery","volume":"11","author":"Clementino","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ijpharm.2008.03.029","article-title":"Intranasal nanoemulsion based brain targeting drug delivery system of risperidone","volume":"358","author":"Kumar","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3109\/10717544.2011.644349","article-title":"Carbamazepine mucoadhesive nanoemulgel (MNEG) as brain targeting delivery system via the olfactory mucosa","volume":"19","author":"Samia","year":"2012","journal-title":"Drug Deliv."},{"key":"ref_116","first-page":"1373","article-title":"Increased brain radioactivity by intranasal P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels","volume":"7","author":"Perez","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.msec.2016.03.015","article-title":"Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route","volume":"63","author":"Jain","year":"2016","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"141","DOI":"10.3109\/08982104.2014.954129","article-title":"Rivastigmine-loaded in situ gelling nanostructured lipid carriers for nose to brain delivery","volume":"25","author":"Wavikar","year":"2015","journal-title":"J. Liposome Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.colsurfb.2016.08.011","article-title":"Fabrication of an ionic-sensitive in situ gel loaded with resveratrol nanosuspensions intended for direct nose-to-brain delivery","volume":"147","author":"Hao","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.ijpharm.2013.05.040","article-title":"Mucus as a barrier to lipophilic drugs","volume":"453","author":"Sigurdsson","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.tcb.2011.06.002","article-title":"Biological hydrogels as selective diffusion barriers","volume":"21","author":"Lieleg","year":"2011","journal-title":"Trends Cell Biol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2008.09.008","article-title":"Barrier properties of mucus","volume":"61","author":"Cone","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.jconrel.2004.04.026","article-title":"Transport of PLA-PEG particles across the nasal mucosa: Effect of particle size and PEG coating density","volume":"98","author":"Vila","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1016\/j.biomaterials.2013.01.064","article-title":"Nanoparticle diffusion in respiratory mucus from humans without lung disease","volume":"34","author":"Schuster","year":"2013","journal-title":"Biomaterials"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"6285","DOI":"10.1016\/j.biomaterials.2011.05.008","article-title":"Drug carrier nanoparticles that penetrate human chronic rhinosinusitis mucus","volume":"32","author":"Lai","year":"2011","journal-title":"Biomaterials"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.jconrel.2011.08.032","article-title":"NANOMEDICINE","volume":"157","author":"Mert","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jconrel.2013.05.035","article-title":"Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus","volume":"170","author":"Xu","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"18355","DOI":"10.1073\/pnas.1214066109","article-title":"Optical tweezers reveal relationship between microstructure and nanoparticle penetration of pulmonary mucus","volume":"109","author":"Kirch","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"557","DOI":"10.2174\/1567201812666150507120124","article-title":"Nose to Brain Delivery of Midazolam Loaded PLGA Nanoparticles: In Vitro and In Vivo Investigations","volume":"13","author":"Sharma","year":"2016","journal-title":"Curr. Drug Deliv."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jconrel.2017.06.032","article-title":"A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles","volume":"261","author":"Sekerdag","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/10611860600721051","article-title":"The brain targeting efficiency following nasally applied MPEG-PLA nanoparticles in rats","volume":"14","author":"Zhang","year":"2006","journal-title":"J. Drug Target."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"9726","DOI":"10.1002\/anie.200803526","article-title":"Addressing the PEG mucoadhesivity paradox to engineer nanoparticles that \u201cslip\u201d through the human mucus barrier","volume":"47","author":"Wang","year":"2008","journal-title":"Angew. Chem."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1023\/A:1019854327540","article-title":"Comparative uptake studies of bioadhesive and non-bioadhesive nanoparticles in human intestinal cell lines and rats: The effect of mucus on particle adsorption and transport","volume":"19","author":"Behrens","year":"2002","journal-title":"Pharm. Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2013\/374252","article-title":"Stealth properties to improve therapeutic efficacy of drug nanocarriers","volume":"2013","author":"Salmaso","year":"2013","journal-title":"J. Drug Deliv."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ejps.2013.02.006","article-title":"The applications of Vitamin E TPGS in drug delivery","volume":"49","author":"Guo","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s11095-009-0041-x","article-title":"Micellar nanocarriers: Potential nose-to-brain delivery of zolmitriptan as novel migraine therapy","volume":"27","author":"Jain","year":"2010","journal-title":"Pharm. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"575","DOI":"10.2217\/nnm.10.28","article-title":"Formulation and evaluation of novel micellar nanocarrier for nasal delivery of sumatriptan","volume":"5","author":"Jain","year":"2010","journal-title":"Nanomedicine"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.colsurfb.2012.05.010","article-title":"Phospholipid based colloidal poloxamer-nanocubic vesicles for brain targeting via the nasal route","volume":"100","author":"Salama","year":"2012","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2017.07.050","article-title":"Response surface optimization, Ex vivo and In vivo investigation of nasal spanlastics for bioavailability enhancement and brain targeting of risperidone","volume":"530","author":"Abdelrahman","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.nano.2013.10.009","article-title":"Gelatin nanostructured lipid carriers-mediated intranasal delivery of basic fibroblast growth factor enhances functional recovery in hemiparkinsonian rats","volume":"10","author":"Zhao","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"931","DOI":"10.3109\/10717544.2014.880860","article-title":"Development, characterization and nasal delivery of rosmarinic acid-loaded solid lipid nanoparticles for the effective management of Huntington\u2019s disease","volume":"22","author":"Bhatt","year":"2015","journal-title":"Drug Deliv."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0168-3659(02)00363-2","article-title":"Nasal drug delivery--possibilities, problems and solutions","volume":"87","author":"Illum","year":"2003","journal-title":"J. Control. Release"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3374","DOI":"10.1080\/10717544.2016.1183721","article-title":"Trans-nasal zolmitriptan novasomes: In vitro preparation, optimization and in vivo evaluation of brain targeting efficiency","volume":"23","author":"Shamma","year":"2016","journal-title":"Drug Deliv."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1007\/s13346-012-0110-2","article-title":"SLN approach for nose-to-brain delivery of alprazolam","volume":"2","author":"Singh","year":"2012","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"369","DOI":"10.4155\/tde.13.6","article-title":"Receptor-based targeting of therapeutics","volume":"4","author":"Mehra","year":"2013","journal-title":"Ther. Deliv."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.jconrel.2009.10.032","article-title":"Nanosystem drug targeting: Facing up to complex realities","volume":"141","author":"Ruenraroengsak","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.addr.2003.10.030","article-title":"Lectin-mediated drug targeting: History and applications","volume":"56","author":"Bies","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1002\/cne.902420410","article-title":"Endocytic and exocytic pathways of the neuronal secretory process and trans synaptic transfer of wheat germ agglutinin-horseradish peroxidasein vivo","volume":"242","author":"Broadwell","year":"1985","journal-title":"J. Comp. Neurol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/0006-8993(95)00637-6","article-title":"Quantitative analysis of the olfactory pathway for drug delivery to the brain","volume":"692","author":"Thorne","year":"1995","journal-title":"Brain Res."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3482","DOI":"10.1016\/j.biomaterials.2006.01.038","article-title":"Lectin-conjugated PEG-PLA nanoparticles: Preparation and brain delivery after intranasal administration","volume":"27","author":"Gao","year":"2006","journal-title":"Biomaterials"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1007\/s11095-011-0641-0","article-title":"Nose-to-brain transport pathways of wheat germ agglutinin conjugated PEG-PLA nanoparticles","volume":"29","author":"Liu","year":"2012","journal-title":"Pharm. Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jconrel.2007.05.026","article-title":"Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration","volume":"121","author":"Gao","year":"2007","journal-title":"J. Control. Release"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1021\/bc8002698","article-title":"Quantum Dots Bearing Lectin-Functionalized Nanoparticles as a Platform for In Vivo Brain Imaging","volume":"19","author":"Gao","year":"2008","journal-title":"Bioconjug. Chem."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3109\/1061186X.2011.622396","article-title":"Solanum tuberosumlectin-conjugated PLGA nanoparticles for nose-to-brain delivery: In vivo and in vitro evaluations","volume":"20","author":"Chen","year":"2011","journal-title":"J. Drug Target."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.ijpharm.2007.03.039","article-title":"UEA I-bearing nanoparticles for brain delivery following intranasal administration","volume":"340","author":"Gao","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3109\/10717544.2011.596583","article-title":"Brain targeting and toxicity study of odorranalectin-conjugated nanoparticles following intranasal administration","volume":"18","author":"Wen","year":"2011","journal-title":"Drug Deliv."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ejpb.2014.02.007","article-title":"Haloperidol-loaded intranasally administered lectin functionalized poly(ethylene glycol)\u2013block-poly(d,l)-lactic-co-glycolic acid (PEG\u2013PLGA) nanoparticles for the treatment of schizophrenia","volume":"87","author":"Piazza","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jconrel.2011.02.022","article-title":"Odorranalectin-conjugated nanoparticles: Preparation, brain delivery and pharmacodynamic study on Parkinson\u2019s disease following intranasal administration","volume":"151","author":"Wen","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.taap.2010.12.003","article-title":"In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain","volume":"251","author":"Liu","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.addr.2009.06.001","article-title":"Recent advances in the use of cell-penetrating peptides for medical and biological applications","volume":"61","author":"Fonseca","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.apsb.2016.04.001","article-title":"Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides","volume":"6","author":"Lin","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"9888","DOI":"10.1016\/j.biomaterials.2011.09.004","article-title":"Low molecular weight protamine-functionalized nanoparticles for drug delivery to the brain after intranasal administration","volume":"32","author":"Xia","year":"2011","journal-title":"Biomaterials"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1007\/s11095-011-0440-7","article-title":"Cell-penetrating peptide-modified block copolymer micelles promote direct brain delivery via intranasal administration","volume":"28","author":"Kanazawa","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.3390\/ph5101092","article-title":"Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors","volume":"5","author":"Taki","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"9220","DOI":"10.1016\/j.biomaterials.2013.08.036","article-title":"Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles","volume":"34","author":"Kanazawa","year":"2013","journal-title":"Biomaterials"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.colsurfb.2017.01.031","article-title":"Nose-to-brain delivery of BACE1 siRNA loaded in solid lipid nanoparticles for Alzheimer\u2019s therapy","volume":"152","author":"Rassu","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"5675","DOI":"10.1073\/pnas.072027199","article-title":"Filamentous phage as vector-mediated antibody delivery to the brain","volume":"99","author":"Frenkel","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_168","unstructured":"Janda, K.J. (2008). Delivery of Active Proteins to the Central Nervous System Using Phage Vectors. (EP 1898701 A1), European Patent."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1007\/s00018-005-5371-1","article-title":"Mammalian lactoferrin receptors: Structure and function","volume":"62","author":"Suzuki","year":"2005","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"3448","DOI":"10.1016\/j.biomaterials.2007.04.011","article-title":"Characterization of lactoferrin as a targeting ligand for nonviral gene delivery to airway epithelial cells","volume":"28","author":"Elfinger","year":"2007","journal-title":"Biomaterials"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.1016\/j.biomaterials.2013.02.003","article-title":"Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration","volume":"34","author":"Liu","year":"2013","journal-title":"Biomaterials"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"6547","DOI":"10.2147\/IJN.S120939","article-title":"Intranasal delivery of rotigotine to the brain with lactoferrin-modified PEG-PLGA nanoparticles for Parkinson\u2019s disease treatment","volume":"11","author":"Bi","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s13346-017-0438-8","article-title":"Intranasal delivery of \u03b1-asarone to the brain with lactoferrin-modified mPEG-PLA nanoparticles prepared by premix membrane emulsification","volume":"8","author":"Pan","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s11051-013-2059-6","article-title":"Transferrin receptor antibody-modified \u03b1-cobrotoxin-loaded nanoparticles enable drug delivery across the blood\u2013brain barrier by intranasal administration","volume":"15","author":"Liu","year":"2013","journal-title":"J. Nanopart. Res."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1002\/jps.24022","article-title":"Aerosol-stable peptide-coated liposome nanoparticles: A proof-of-concept study with opioid fentanyl in enhancing analgesic effects and reducing plasma drug exposure","volume":"103","author":"Hoekman","year":"2014","journal-title":"J. Pharm. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/10\/1\/34\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:57:13Z","timestamp":1760194633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/10\/1\/34"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,15]]},"references-count":175,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,3]]}},"alternative-id":["pharmaceutics10010034"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics10010034","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints201802.0077.v1","asserted-by":"object"}]},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,15]]}}}