{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:02:24Z","timestamp":1789596144130,"version":"build-2803163510"},"reference-count":242,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Malaysia Pahang Al-Sultan Abdullah"},{"id":[{"id":"https:\/\/ror.org\/01704wp68","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"crossref","award":["FRGS\/1\/2024\/TK09\/UMP\/02\/6"],"award-info":[{"award-number":["FRGS\/1\/2024\/TK09\/UMP\/02\/6"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FRGS\/1\/2024\/TK09\/UMP\/02\/6"],"award-info":[{"award-number":["FRGS\/1\/2024\/TK09\/UMP\/02\/6"]}],"id":[{"id":"https:\/\/ror.org\/05mcs2t73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Nose-to-brain (N2B) delivery is a practical, non-invasive strategy for CNS targeting that can increase brain exposure while limiting systemic exposure. This review integrates three milestones in N2B delivery, formulations, devices, and quantitative evaluation strategies, to define design rules for effective olfactory\/trigeminal deposition and enhance translational relevance. Formulations emphasize mucoadhesive systems, nanoparticle carriers (polymeric, lipid-based, and hybrid), nano-emulsions, and stimuli-responsive \u201csmart\u201d gels that prolong nasal residence. Regarding device advancements, the review covers conventional nasal sprays optimized for plume geometry and droplet size. Furthermore, it examines breath-actuated metered sprays, which promote soft palate closure to route aerosols to superior regions, and vibrating mesh nebulizers capable of low-velocity mists for improved upper cavity deposition. Quantitative evaluation is discussed, including 3D-printed, anatomy-accurate nasal casts, high-speed spray diagnostics, and computational fluid dynamics (CFD). This review further links formulation and device parameters to regional deposition. Available clinical and animal data illustrate the feasibility of these approaches, safety considerations, and user-technique dependencies, while highlighting the need for standardized, anatomy-aware testing protocols. Together, these developments suggest that co-designed formulation device platforms, validated by cast\/CFD metrics and supported by clinical imaging or pharmacokinetic data, can support N2B product development toward consistent, patient-relevant outcomes.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070902","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T01:01:28Z","timestamp":1784768488000},"page":"902","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Advances in Intranasal CNS Targeting: Integrating Formulations, Devices, Computational Fluid Dynamics, and 3D Printing"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0240-6816","authenticated-orcid":false,"given":"Lena","family":"Shaghlil","sequence":"first","affiliation":[{"name":"Faculty of Mechanical and Automotive Engineering Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Pekan 26600, Pahang, Malaysia"},{"name":"Center for Research in Advanced Fluid & Processes, Universiti Malaysia Pahang Al-Sultan Abdullah, Kuantan 26300, Pahang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-651X","authenticated-orcid":false,"given":"Yousef","family":"Al-Ebini","sequence":"additional","affiliation":[{"name":"Department of Cosmetic Science, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud J. Al","family":"Shawabkeh","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery and Diagnostic Sciences, Applied Science Private University, Amman 11937, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatmawati","family":"Adam","sequence":"additional","affiliation":[{"name":"Center for Research in Advanced Fluid & Processes, Universiti Malaysia Pahang Al-Sultan Abdullah, Kuantan 26300, Pahang, Malaysia"},{"name":"Faculty of Chemical and Process Engineering Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Kuantan 26300, Pahang, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-5113","authenticated-orcid":false,"given":"Kuldeep K.","family":"Saxena","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Bennett University, Greater Noida 201310, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0040-5492","authenticated-orcid":false,"given":"Anas","family":"Alshishani","sequence":"additional","affiliation":[{"name":"Research and Development Department, PharmaPrimes Lab, Amman 11190, Jordan"},{"name":"Pharmaceutical Research Center, Zarqa University, Zarqa 13110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1673-5584","authenticated-orcid":false,"given":"Wan Sharuzi","family":"Wan Harun","sequence":"additional","affiliation":[{"name":"Faculty of Mechanical and Automotive Engineering Technology, Universiti Malaysia Pahang Al-Sultan Abdullah, Pekan 26600, Pahang, Malaysia"},{"name":"Faculty of Artificial Intelligence and Cybersecurity, Universiti Teknikal Malaysia Melaka, Durian Tunggal 76100, Melaka, Malaysia"},{"name":"Department of Mechanical Engineering, Universitas Negeri Jakarta, Jl. Rawamangun Muka, Jakarta 13220, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/S1474-4422(24)00038-3","article-title":"Global, Regional, and National Burden of Disorders Affecting the Nervous System, 1990\u20132021: A Systematic Analysis for the Global Burden of Disease Study 2021","volume":"23","author":"Steinmetz","year":"2024","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"102225","DOI":"10.1016\/j.gde.2024.102225","article-title":"Circuit Integration by Transplanted Human Neurons","volume":"89","author":"Yuan","year":"2024","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gandhi, S., Shastri, D.H., Shah, J., Nair, A.B., and Jacob, S. (2024). 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