{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:05:07Z","timestamp":1792202707673,"version":"4.4.0"},"reference-count":234,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cRicerca Corrente\u201d funding scheme of the Italian Ministry of Health"},{"name":"JPND 2022","award":["ERP-2022-23682561\u2014ERP-2022-JPND 22-DC4MND"],"award-info":[{"award-number":["ERP-2022-23682561\u2014ERP-2022-JPND 22-DC4MND"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>While the Blood\u2013Brain Barrier (BBB) is essential for the protection and function of the Central Nervous System (CNS), it also represents a challenge for drug delivery in the treatment of CNS disorders due to its limited permeability and high expression of efflux transporters. Crossing the BBB becomes even more difficult when dealing with biomolecular therapeutics (e.g., monoclonal antibodies and Antisense Oligonucleotides) due to their hydrophilic nature and high molecular weight. Over the years, different strategies have been developed in order to maximize the ability of biopharmaceuticals to cross the BBB and be delivered to the CNS. Both non-invasive techniques, mainly consisting of developing innovative vectors or using non-conventional routes of administration (e.g., intranasal delivery), and invasive methods, such as intracerebroventricular\/intrathecal administration, have been tested individually and in combination. Given the improvements achieved nowadays with both approaches, here, we plan to compare the advances in invasive techniques, such as those based on the use of device-assisted strategies, and the employment of the intranasal route of administration. We are also interested in reporting the applicability of both strategies in the treatment of aggressive forms of cancer, such as glioblastoma, as well as neurodegenerative diseases, in order to determine which technique can be considered a better choice in each specific case.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040484","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T14:24:58Z","timestamp":1776176698000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Intranasal vs. Device-Assisted Drug Delivery: Advantages and Limitations for the Delivery of Biopharmaceuticals to the CNS"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9931-7849","authenticated-orcid":false,"given":"Lisa Benedetta","family":"De Martini","sequence":"first","affiliation":[{"name":"National Center for Oncological Hadrontherapy (CNAO), 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5993-6522","authenticated-orcid":false,"given":"Chiara Flora","family":"Valori","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Morrone","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Brambilla","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-1327","authenticated-orcid":false,"given":"Daniela","family":"Rossi","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Laboratory for Research on Neurodegenerative Disorders, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41573-021-00139-y","article-title":"Strategies for Delivering Therapeutics across the Blood\u2013Brain Barrier","volume":"20","author":"Terstappen","year":"2021","journal-title":"Nat. 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