{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:37:17Z","timestamp":1793745437974,"version":"4.6.1"},"reference-count":118,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Council for Scientific and Technological Development","award":["442425\/2020-1"],"award-info":[{"award-number":["442425\/2020-1"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Council for Scientific and Technological Development","award":["443999\/2023-66"],"award-info":[{"award-number":["443999\/2023-66"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Council for Scientific and Technological Development","award":["403587\/2021-2"],"award-info":[{"award-number":["403587\/2021-2"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Council for Scientific and Technological Development","award":["23\/2551-0000906-4"],"award-info":[{"award-number":["23\/2551-0000906-4"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Council for Scientific and Technological Development","award":["20220602"],"award-info":[{"award-number":["20220602"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Council for Scientific and Technological Development","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Rio Grande do Sul Research Foundation","award":["442425\/2020-1"],"award-info":[{"award-number":["442425\/2020-1"]}]},{"name":"Rio Grande do Sul Research Foundation","award":["443999\/2023-66"],"award-info":[{"award-number":["443999\/2023-66"]}]},{"name":"Rio Grande do Sul Research Foundation","award":["403587\/2021-2"],"award-info":[{"award-number":["403587\/2021-2"]}]},{"name":"Rio Grande do Sul Research Foundation","award":["23\/2551-0000906-4"],"award-info":[{"award-number":["23\/2551-0000906-4"]}]},{"name":"Rio Grande do Sul Research Foundation","award":["20220602"],"award-info":[{"award-number":["20220602"]}]},{"name":"Rio Grande do Sul Research Foundation","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["442425\/2020-1"],"award-info":[{"award-number":["442425\/2020-1"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["443999\/2023-66"],"award-info":[{"award-number":["443999\/2023-66"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["403587\/2021-2"],"award-info":[{"award-number":["403587\/2021-2"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["23\/2551-0000906-4"],"award-info":[{"award-number":["23\/2551-0000906-4"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["20220602"],"award-info":[{"award-number":["20220602"]}]},{"name":"Coordination for the Improvement of Higher Education Personnel\u2014Brazil","award":["001"],"award-info":[{"award-number":["001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>The nasal route represents a promising non-invasive technique for the direct delivery of nucleic acids to the central nervous system (CNS) disorders, effectively bypassing the blood\u2013brain barrier. This route offers several advantages, including ease of administration, enhanced patient compliance, rapid therapeutic onset, and increased availability. Nonetheless, challenges such as mucociliary clearance, enzymatic degradation, and the low permeability of cell membranes to large molecules remain obstacles to the effectiveness of this approach. To address these limitations and achieve targeted nose-to-brain delivery with optimized therapeutic outcomes, various technological solutions have been explored, such as nanotechnology-based delivery systems and mucoadhesive formulations. These innovations aim to enhance the permeability of the nasal mucosa, extend the residence time of therapeutic agents in the nasal cavity, and improve overall treatment effectiveness. While the nasal gene delivery to the brain is still relatively new, it holds considerable potential for expanding treatment options for a range of CNS disorders. In this context, this review examines the anatomy and physiology of the nasal route, the mechanisms of biomolecule transport from nose to brain, the potential of gene delivery vectors, key preclinical advancements, and clinical perspectives for the nasal delivery of nucleic acids in CNS disorders.<\/jats:p>","DOI":"10.3390\/pharmaceutics17091177","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T08:43:54Z","timestamp":1757493834000},"page":"1177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Recent Advances in Nose-to-Brain Gene Delivery for Central Nervous System Disorders"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-9497","authenticated-orcid":false,"given":"Fl\u00e1via Nathiely Silveira","family":"Fachel","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Salatino-Oliveira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2820-2814","authenticated-orcid":false,"given":"Willian da Silva","family":"Carniel","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4977-6662","authenticated-orcid":false,"given":"Ursula","family":"Matte","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, Brazil"},{"name":"Laborat\u00f3rio C\u00e9lulas, Tecidos e Genes, Servi\u00e7o de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre 90410-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder Ferreira","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-5861","authenticated-orcid":false,"given":"Guilherme","family":"Baldo","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, RS, Brazil"},{"name":"Laborat\u00f3rio C\u00e9lulas, Tecidos e Genes, Servi\u00e7o de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre 90410-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4189-0436","authenticated-orcid":false,"given":"Roselena Silvestri","family":"Schuh","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal do Rio Grande do Sul, Porto Alegre 90610-000, RS, Brazil"},{"name":"Laborat\u00f3rio C\u00e9lulas, Tecidos e Genes, Servi\u00e7o de Pesquisa Experimental, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre 90410-000, RS, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.jconrel.2017.09.001","article-title":"Progress in Brain Targeting Drug Delivery System by Nasal Route","volume":"268","author":"Khan","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Shah, P., Lalan, M., and Barve, K. (2022). Intranasal Delivery: An Attractive Route for the Administration of Nucleic Acid Based Therapeutics for CNS Disorders. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.974666"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/j.addr.2011.11.002","article-title":"Intranasal Delivery of Biologics to the Central Nervous System","volume":"64","author":"Lochhead","year":"2012","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.pharmthera.2012.03.003","article-title":"Intranasal Drug Delivery: An Efficient and Non-Invasive Route for Systemic Administration-Focus on Opioids","volume":"134","author":"Buenestado","year":"2012","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Duong, V.-A., Nguyen, T.-T.-L., and Maeng, H.-J. (2023). Recent Advances in Intranasal Liposomes for Drug, Gene, and Vaccine Delivery. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010207"},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"Berillo, D., Zharkinbekov, Z., Kim, Y., Raziyeva, K., Temirkhanova, K., and Saparov, A. (2021). Stimuli-Responsive Polymers for Transdermal, Transmucosal and Ocular Drug Delivery. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13122050"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.addr.2008.09.005","article-title":"Nanoparticles for Nasal Vaccination","volume":"61","author":"Csaba","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"120994","DOI":"10.1016\/j.ijpharm.2021.120994","article-title":"Progress in Nasal Drug Delivery Systems","volume":"607","author":"Laffleur","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Protopapa, C., Siamidi, A., Pavlou, P., and Vlachou, M. (2022). Excipients Used for Modified Nasal Drug Delivery: A Mini-Review of the Recent Advances. Materials, 15.","DOI":"10.3390\/ma15196547"},{"key":"ref_12","first-page":"43","article-title":"Nasal Drug Delivery\u2013As an Effective Tool for Brain Targeting-A Review","volume":"1","author":"Paun","year":"2010","journal-title":"Int. J. Pharm. Appl. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.33786\/JCPR.2014.v04i03.008","article-title":"Nasal Drug Delivery: Problem Solution and Its Application","volume":"4","author":"Mujawar","year":"2014","journal-title":"J. Curr. Pharma Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1007\/s13346-024-01770-z","article-title":"Revolutionizing Parkinson\u2019s Treatment: Harnessing the Potential of Intranasal Nanoemulsions for Targeted Therapy","volume":"15","author":"Sharma","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1007\/s13346-021-01086-2","article-title":"Using Nanotechnology to Deliver Biomolecules from Nose to Brain\u2014Peptides, Proteins, Monoclonal Antibodies and RNA","volume":"12","author":"Borrajo","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Patharapankal, E.J., Ajiboye, A.L., Mattern, C., and Trivedi, V. (2024). Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010066"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.brainresbull.2018.10.009","article-title":"Evaluation of Intranasal Delivery Route of Drug Administration for Brain Targeting","volume":"143","author":"Bors","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"619","DOI":"10.2174\/1381612828666211222163025","article-title":"Drug Delivery Systems and Strategies to Overcome the Barriers of Brain","volume":"28","author":"Garg","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jconrel.2018.10.004","article-title":"Recent Progress of Drug Nanoformulations Targeting to Brain","volume":"291","author":"Khan","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s40005-022-00589-5","article-title":"Drug Delivery to the Brain via the Nasal Route of Administration: Exploration of Key Targets and Major Consideration Factors","volume":"53","author":"Jeong","year":"2023","journal-title":"J. Pharm. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1007\/s11095-022-03433-5","article-title":"CNS Delivery of Nucleic Acid Therapeutics: Beyond the Blood\u2013Brain Barrier and Towards Specific Cellular Targeting","volume":"40","author":"Nozohouri","year":"2023","journal-title":"Pharm. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1038\/s41565-021-00898-0","article-title":"The Current Landscape of Nucleic Acid Therapeutics","volume":"16","author":"Kulkarni","year":"2021","journal-title":"Nat. Nanotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Geng, G., Xu, Y., Hu, Z., Wang, H., Chen, X., Yuan, W., and Shu, Y. (2025). Viral and Non-Viral Vectors in Gene Therapy: Current State and Clinical Perspectives. EBioMedicine, 118.","DOI":"10.1016\/j.ebiom.2025.105834"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115363","DOI":"10.1016\/j.addr.2024.115363","article-title":"Adeno-Associated Virus Vector Delivery to the Brain: Technology Advancements and Clinical Applications","volume":"211","author":"Ye","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neuropharm.2016.02.013","article-title":"Viral Vectors for Therapy of Neurologic Diseases","volume":"120","author":"Choudhury","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_27","first-page":"1012","article-title":"Utilizing Mucoadhesive Polymers for Nasal Drug Delivery System","volume":"8","author":"Kirange","year":"2017","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.ijpharm.2017.10.030","article-title":"Cationic Nanoemulsions as Nucleic Acids Delivery Systems","volume":"534","author":"Teixeira","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1039\/C9BM01112A","article-title":"Ligand Targeting and Peptide Functionalized Polymers as Non-Viral Carriers for Gene Therapy","volume":"8","author":"Muhammad","year":"2020","journal-title":"Biomater. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1080\/17425247.2016.1202235","article-title":"Nanotechnology Applied to Treatment of Mucopolysaccharidoses","volume":"13","author":"Schuh","year":"2016","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.nano.2015.12.374","article-title":"Intranasal Brain Delivery of Cationic Nanoemulsion-Encapsulated TNFalpha SiRNA in Prevention of Experimental Neuroinflammation","volume":"12","author":"Yadav","year":"2016","journal-title":"Nanomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Taylor, R.E., and Zahid, M. (2020). Cell Penetrating Peptides, Novel Vectors for Gene Therapy. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12030225"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1248\/cpb.53.871","article-title":"Lipid Carrier Systems for Targeted Drug and Gene Delivery","volume":"53","author":"Hashida","year":"2005","journal-title":"Chem. Pharm. Bull."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"56","DOI":"10.2741\/s526","article-title":"Delivery of SiRNA Therapeutics: PLGA Nanoparticles Approach","volume":"11","author":"Matta","year":"2019","journal-title":"Front. Biosci. (Sch. Ed)"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1517\/17425240903241796","article-title":"Non-Viral Gene Delivery Using Nanoparticles","volume":"6","author":"Ditto","year":"2009","journal-title":"Expert. Opin. Drug Deliv."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bonferoni, M.C., Rossi, S., Sandri, G., Ferrari, F., Gavini, E., Rassu, G., and Giunchedi, P. (2019). Nanoemulsions for \u201cNose-to-Brain\u201d Drug Delivery. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020084"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1021\/mp4005029","article-title":"Formulation and Characterization of Nanoemulsion Intranasal Adjuvants: Effects of Surfactant Composition on Mucoadhesion and Immunogenicity","volume":"11","author":"Wong","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.colsurfb.2010.05.026","article-title":"Cationic Nanoemulsions as Non-Viral Vectors for Plasmid DNA Delivery","volume":"79","author":"Liu","year":"2010","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41434-019-0113-4","article-title":"Neonatal Nonviral Gene Editing with the CRISPR\/Cas9 System Improves Some Cardiovascular, Respiratory, and Bone Disease Features of the Mucopolysaccharidosis I Phenotype in Mice","volume":"27","author":"Schuh","year":"2020","journal-title":"Gene Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.jcis.2018.06.058","article-title":"Physicochemical Properties of Cationic Nanoemulsions and Liposomes Obtained by Microfluidization Complexed with a Single Plasmid or along with an Oligonucleotide: Implications for CRISPR\/Cas Technology","volume":"530","author":"Schuh","year":"2018","journal-title":"J. Colloid. Interface Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ejpb.2017.10.017","article-title":"Gene Editing of MPS I Human Fibroblasts by Co-Delivery of a CRISPR\/Cas9 Plasmid and a Donor Oligonucleotide Using Nanoemulsions as Nonviral Carriers","volume":"122","author":"Schuh","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbamem.2004.02.007","article-title":"Transfection Efficiency and Cytotoxicity of Cationic Liposomes in Salmonid Cell Lines of Hepatocyte and Macrophage Origin","volume":"1663","author":"Thu","year":"2004","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s11095-018-2503-5","article-title":"Nasal Administration of Cationic Nanoemulsions as Nucleic Acids Delivery Systems Aiming at Mucopolysaccharidosis Type I Gene Therapy","volume":"35","author":"Schuh","year":"2018","journal-title":"Pharm. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e3410","DOI":"10.1002\/jgm.3410","article-title":"Brain and Visceral Gene Editing of Mucopolysaccharidosis I Mice by Nasal Delivery of the CRISPR\/Cas9 System","volume":"24","author":"Vera","year":"2022","journal-title":"J. Gene Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1007\/s12035-019-01730-6","article-title":"Nasal Administration of Cationic Nanoemulsions as CD73-SiRNA Delivery System for Glioblastoma Treatment: A New Therapeutical Approach","volume":"57","author":"Azambuja","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1021\/acs.molpharmaceut.0c00170","article-title":"Intranasal Delivery and Transfection of MRNA Therapeutics in the Brain Using Cationic Liposomes","volume":"17","author":"Dhaliwal","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1211\/002235702320402035","article-title":"Intranasal Administration of Plasmid DNA-Coated Nanoparticles Results in Enhanced Immune Responses","volume":"54","author":"Cui","year":"2002","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Rodriguez, M., Lapierre, J., Ojha, C., Kaushik, A., Batrakova, E., Kashanchi, F., Dever, S., Nair, M., and El-Hage, N. (2017). Intranasal Drug Delivery of Small Interfering RNA Targeting Beclin1 Encapsulated with Polyethylenimine (PEI) in Mouse Brain to Achieve HIV Attenuation. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-01819-9"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"102857","DOI":"10.1016\/j.ijadhadh.2021.102857","article-title":"Mucoadhesive Properties of Polyacrylates: Structure\u2013Function Relationship","volume":"107","author":"Lam","year":"2021","journal-title":"Int. J. Adhes. Adhes."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1002\/jps.21887","article-title":"Thiolated Polycarbophil as an Adjuvant for Permeation Enhancement in Nasal Delivery of Antisense Oligonucleotides","volume":"99","author":"Vetter","year":"2010","journal-title":"J. Pharm. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3109\/10611860903450031","article-title":"Nasal Delivery of Antisense Oligonucleotides: In Vitro Evaluation of a Thiomer\/Glutathione Microparticulate Delivery System","volume":"18","author":"Vetter","year":"2010","journal-title":"J. Drug Target."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.colsurfb.2007.04.009","article-title":"Chitosan Nanoparticle as Protein Delivery Carrier\u2014Systematic Examination of Fabrication Conditions for Efficient Loading and Release","volume":"59","author":"Gan","year":"2007","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"102119","DOI":"10.1016\/j.nano.2019.102119","article-title":"Enriched Chitosan Nanoparticles Loaded with SiRNA Are Effective in Lowering Huntington\u2019s Disease Gene Expression Following Intranasal Administration","volume":"24","author":"Sava","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.jconrel.2008.11.021","article-title":"Nucleic Acid Delivery with Chitosan and Its Derivatives","volume":"134","author":"Lai","year":"2009","journal-title":"J. Control Release"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.addr.2009.08.004","article-title":"Chitosan-Based Formulations for Delivery of DNA and SiRNA","volume":"62","author":"Mao","year":"2010","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2003.12.026","article-title":"Chitosan Microspheres as a Potential Carrier for Drugs","volume":"274","author":"Sinha","year":"2004","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"195","DOI":"10.15171\/apb.2019.023","article-title":"Current Advances in Chitosan Nanoparticles Based Drug Delivery and Targeting","volume":"9","author":"Garg","year":"2019","journal-title":"Adv. Pharm. Bull."},{"key":"ref_59","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_60","doi-asserted-by":"crossref","unstructured":"Russo, E., and Villa, C. (2019). Poloxamer Hydrogels for Biomedical Applications. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11120671"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Rodriguez-Otormin, F., Duro Casta\u00f1o, A., Conejos-Sanchez, I., and Vicent, M. (2018). Envisioning the Future of Polymer Therapeutics for Brain Disorders. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol, 11.","DOI":"10.1002\/wnan.1532"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/jbm.1227","article-title":"In Situ Gelling and Mucoadhesive Polymer Vehicles for Controlled Intranasal Delivery of Plasmid DNA","volume":"59","author":"Park","year":"2002","journal-title":"J. Biomed. Mater. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jconrel.2021.12.034","article-title":"Enhanced Nose-to-Brain Delivery of SiRNA Using Hyaluronan-Enveloped Nanomicelles for Glioma Therapy","volume":"342","author":"Yang","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_64","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_65","doi-asserted-by":"crossref","unstructured":"Muolokwu, C.E., Chaulagain, B., Gothwal, A., Mahanta, A.K., Tagoe, B., Lamsal, B., and Singh, J. (2024). Functionalized Nanoparticles to Deliver Nucleic Acids to the Brain for the Treatment of Alzheimer\u2019s Disease. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1405423"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Su, Y., Sun, B., Gao, X., Dong, X., Fu, L., Zhang, Y., Li, Z., Wang, Y., Jiang, H., and Han, B. (2020). Intranasal Delivery of Targeted Nanoparticles Loaded with MiR-132 to Brain for the Treatment of Neurodegenerative Diseases. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.01165"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ejpb.2018.11.017","article-title":"Solid Lipid Nanoparticles for the Delivery of Anti-Microbial Oligonucleotides","volume":"134","author":"Sitia","year":"2019","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1016\/j.colsurfb.2014.01.053","article-title":"Charge-Mediated Topical Delivery of Plasmid DNA with Cationic Lipid Nanoparticles to the Skin","volume":"116","author":"Jin","year":"2014","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_69","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_70","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.copbio.2013.11.014","article-title":"Biological Nanoparticles and Their Influence on Organisms","volume":"28","author":"Stanley","year":"2014","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Hasan, A., Nejadi Babadaei, M.M., Behzadi, E., Nouri, M., Sharifi, M., and Falahati, M. (2020). Exosomes: Multiple-Targeted Multifunctional Biological Nanoparticles in the Diagnosis, Drug Delivery, and Imaging of Cancer Cells. Biomed. Pharmacother., 129.","DOI":"10.1016\/j.biopha.2020.110442"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"53177","DOI":"10.1021\/acsami.3c08756","article-title":"Enhanced Nose-to-Brain Delivery of Combined Small Interfering RNAs Using Lesion-Recognizing Nanoparticles for the Synergistic Therapy of Alzheimer\u2019s Disease","volume":"15","author":"Li","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1517\/14712598.2015.1014794","article-title":"Immunological and Hematological Toxicities Challenging Clinical Translation of Nucleic Acid-Based Therapeutics","volume":"15","author":"Dobrovolskaia","year":"2015","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"103371","DOI":"10.1016\/j.drudis.2022.103371","article-title":"Intranasal Delivery of Biotechnology-Based Therapeutics","volume":"27","author":"Patel","year":"2022","journal-title":"Drug Discov. Today"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/gt.2014.28","article-title":"Intranasal Administration of Plasmid DNA Nanoparticles Yields Successful Transfection and Expression of a Reporter Protein in Rat Brain","volume":"21","author":"Harmon","year":"2014","journal-title":"Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.nano.2018.11.006","article-title":"Intranasal Delivery of HGDNF Plasmid DNA Nanoparticles Results in Long-Term and Widespread Transfection of Perivascular Cells in Rat Brain","volume":"16","author":"Aly","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jddst.2017.11.013","article-title":"Chitosan-Mangafodipir Nanoparticles Designed for Intranasal Delivery of SiRNA and DNA to Brain","volume":"43","author":"Song","year":"2018","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Petkova, A.I., Kubajewska, I., Vaideanu, A., Sch\u00e4tzlein, A.G., and Uchegbu, I.F. (2022). Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061136"},{"key":"ref_79","first-page":"1","article-title":"VGF-Derived Peptide TLQP-21 Modulates Microglial Function through C3aR1 Signaling Pathways and Reduces Neuropathology in 5xFAD Mice","volume":"15","author":"Audrain","year":"2020","journal-title":"Mol. Neurodegener."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Lamptey, R.N.L., Gothwal, A., Trivedi, R., Arora, S., and Singh, J. (2022). Synthesis and Characterization of Fatty Acid Grafted Chitosan Polymeric Micelles for Improved Gene Delivery of VGF to the Brain through Intranasal Route. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020493"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.jconrel.2021.01.027","article-title":"Minimally Invasive Nasal Depot (MIND) Technique for Direct BDNF AntagoNAT Delivery to the Brain","volume":"331","author":"Padmakumar","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.jad.2014.11.044","article-title":"BDNF as a Biomarker for Successful Treatment of Mood Disorders: A Systematic & Quantitative Meta-Analysis","volume":"174","author":"Polyakova","year":"2015","journal-title":"J. Affect. Disord."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Kishi, T., Yoshimura, R., Ikuta, T., and Iwata, N. (2018). Brain-Derived Neurotrophic Factor and Major Depressive Disorder: Evidence from Meta-Analyses. Front. Psychiatry, 8.","DOI":"10.3389\/fpsyt.2017.00308"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1016\/j.nano.2014.01.003","article-title":"Magnetic Micelles for DNA Delivery to Rat Brains after Mild Traumatic Brain Injury","volume":"10","author":"Das","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/gt.2017.55","article-title":"Nasal Application of HSV Encoding Human Preproenkephalin Blocks Craniofacial Pain in a Rat Model of Traumatic Brain Injury","volume":"24","author":"Meidahl","year":"2017","journal-title":"Gene Ther."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s12035-014-9070-5","article-title":"Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases","volume":"53","author":"Tang","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/j.neuropharm.2018.05.002","article-title":"Intranasally Delivered Small Interfering RNA-Mediated Suppression of Scavenger Receptor Mac-1 Attenuates Microglial Phenotype Switching and Working Memory Impairment Following Hypoxia","volume":"137","author":"Das","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Kozuka, T., Omori, Y., Watanabe, S., Tarusawa, E., Yamamoto, H., Chaya, T., Furuhashi, M., Morita, M., Sato, T., and Hirose, S. (2019). MiR-124 Dosage Regulates Prefrontal Cortex Function by Dopaminergic Modulation. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-38910-2"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.biomaterials.2016.03.025","article-title":"MiRNA-124 Induces Neuroprotection and Functional Improvement after Focal Cerebral Ischemia","volume":"91","author":"Kho","year":"2016","journal-title":"Biomaterials"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1080\/10717544.2020.1760960","article-title":"RVG29-Modified MicroRNA-Loaded Nanoparticles Improve Ischemic Brain Injury by Nasal Delivery","volume":"27","author":"Hao","year":"2020","journal-title":"Drug Deliv."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10015","DOI":"10.1021\/acsnano.9b01892","article-title":"Intranasal Delivery of Mesenchymal Stem Cell Derived Exosomes Loaded with Phosphatase and Tensin Homolog SiRNA Repairs Complete Spinal Cord Injury","volume":"13","author":"Guo","year":"2019","journal-title":"ACS Nano"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"9306","DOI":"10.1523\/JNEUROSCI.6271-09.2010","article-title":"PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons","volume":"30","author":"Christie","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/jgm.993","article-title":"Nasal Inoculation of an Adenovirus Vector Encoding 11 Tandem Repeats of A\u03b21--6 Upregulates IL--10 Expression and Reduces Amyloid Load in a Mo\/Hu APPswe PS1dE9 Mouse Model of Alzheimer\u2019s Disease","volume":"9","author":"Kim","year":"2007","journal-title":"J. Gene Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1385\/MN:26:2-3:283","article-title":"Hypoxia Signaling to Genes: Significance in Alzheimer\u2019s Disease","volume":"26","author":"Bazan","year":"2002","journal-title":"Mol. Neurobiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/j.1749-6632.2009.05026.x","article-title":"Hypoxia and Neurodegeneration","volume":"1177","author":"Peers","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2208","DOI":"10.1089\/ars.2014.5845","article-title":"CD36 Upregulation Mediated by Intranasal LV-NRF2 Treatment Mitigates Hypoxia-Induced Progression of Alzheimer\u2019s-Like Pathogenesis","volume":"21","author":"Wang","year":"2014","journal-title":"Antioxid. Redox Signal"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"563","DOI":"10.3233\/JAD-150395","article-title":"MiRNAs: Key Players in Neurodegenerative Disorders and Epilepsy","volume":"48","author":"Karnati","year":"2015","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2174\/2211536606666170811151503","article-title":"Environment and Neurodegenerative Diseases: An Update on MiRNA Role","volume":"6","author":"Ferrante","year":"2017","journal-title":"MicroRNA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"\u03b1-Synuclein in Lewy Bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"II3","DOI":"10.1007\/PL00007758","article-title":"Pathoanatomy of Parkinson\u2019s Disease","volume":"247","author":"Braak","year":"2000","journal-title":"J. Neurol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ymthe.2017.11.015","article-title":"Selective \u03b1-Synuclein Knockdown in Monoamine Neurons by Intranasal Oligonucleotide Delivery: Potential Therapy for Parkinson\u2019s Disease","volume":"26","author":"Recasens","year":"2018","journal-title":"Mol. Ther."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1007\/s12035-018-1109-6","article-title":"Intranasal Delivery of PGDNF DNA Nanoparticles Provides Neuroprotection in the Rat 6-Hydroxydopamine Model of Parkinson\u2019s Disease","volume":"56","author":"Aly","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/0006-8993(94)01366-P","article-title":"GDNF Protects Nigral Dopamine Neurons against 6-Hydroxydopamine in vivo","volume":"672","author":"Kearns","year":"1995","journal-title":"Brain Res."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nn1175","article-title":"Localized Striatal Delivery of GDNF as a Treatment for Parkinson Disease","volume":"7","author":"Kirik","year":"2004","journal-title":"Nat. Neurosci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"102517","DOI":"10.1016\/j.jddst.2021.102517","article-title":"Kinetics of HTT Lowering in Brain of YAC 128 Mice Following Single and Repetitive Intranasal Dosing of SiRNA Packaged in Chitosan-Based Nanoparticles","volume":"63","author":"Sava","year":"2021","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"123343","DOI":"10.1016\/j.ijpharm.2023.123343","article-title":"Dose-Dependent Delivery of Genes to the Cerebral Cortex via the Nasal Route","volume":"644","author":"Fatani","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1038\/mt.2015.188","article-title":"Grapefruit-Derived Nanovectors Delivering Therapeutic MiR17 Through an Intranasal Route Inhibit Brain Tumor Progression","volume":"24","author":"Zhuang","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Sukumar, U.K., Bose, R.J.C., Malhotra, M., Babikir, H.A., Afjei, R., Robinson, E., Zeng, Y., Chang, E., Habte, F., and Sinclair, R. (2019). Intranasal Delivery of Targeted Polyfunctional Gold\u2013Iron Oxide Nanoparticles Loaded with Therapeutic MicroRNAs for Combined Theranostic Multimodality Imaging and Presensitization of Glioblastoma to Temozolomide. Biomaterials, 218.","DOI":"10.1016\/j.biomaterials.2019.119342"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.actbio.2021.10.042","article-title":"Core-Shell Lipoplexes Inducing Active Macropinocytosis Promote Intranasal Delivery of c-Myc SiRNA for Treatment of Glioblastoma","volume":"138","author":"Hu","year":"2022","journal-title":"Acta Biomater."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major Depressive Disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.neuroscience.2015.05.053","article-title":"Pathogenesis of Depression: Insights from Human and Rodent Studies","volume":"321","author":"Hodes","year":"2016","journal-title":"Neuroscience"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Ma, X., Liu, P., Zhang, X., Jiang, W., Jia, M., Wang, C., Dong, Y., Dang, Y., and Gao, C. (2016). Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: A Potential Promising Therapy Strategy for Major Depressive Disorder. Sci. Rep., 6.","DOI":"10.1038\/srep22404"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"637","DOI":"10.2147\/NDT.S227598","article-title":"A Study of Antidepressant Effect and Mechanism on Intranasal Delivery of BDNF-HA2TAT\/AAV to Rats with Post-Stroke Depression","volume":"16","author":"Chen","year":"2020","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1159\/000528755","article-title":"Brain-Derived Neurotrophic Factor Delivered Intranasally Relieves Post-Traumatic Stress Disorder Symptoms Caused by a Single Prolonged Stress in Rats","volume":"82","author":"Zhang","year":"2023","journal-title":"Neuropsychobiology"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Kubaski, F., de Oliveira Poswar, F., Michelin-Tirelli, K., da Silveira Matte, U., Horovitz, D.D., Barth, A.L., Baldo, G., Vairo, F., and Giugliani, R. (2020). Mucopolysaccharidosis Type I. Diagnostics, 10.","DOI":"10.3390\/diagnostics10030161"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1089\/hum.2017.187","article-title":"Intranasal Adeno-Associated Virus Mediated Gene Delivery and Expression of Human Iduronidase in the Central Nervous System: A Noninvasive and Effective Approach for Prevention of Neurologic Disease in Mucopolysaccharidosis Type I","volume":"28","author":"Belur","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.jconrel.2024.01.027","article-title":"Investigating the Efficacy of Nasal Administration for Delivering Magnetic Nanoparticles into the Brain for Magnetic Particle Imaging","volume":"367","author":"Seino","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jconrel.2023.12.054","article-title":"Nanotechnology for Enhanced Nose-to-Brain Drug Delivery in Treating Neurological Diseases","volume":"366","author":"Huang","year":"2024","journal-title":"J. Control. Release"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/9\/1177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:43:00Z","timestamp":1760035380000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/9\/1177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,10]]},"references-count":118,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["pharmaceutics17091177"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17091177","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,10]]}}}