{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:31:01Z","timestamp":1786375861872,"version":"build-2736575974"},"reference-count":63,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T00:00:00Z","timestamp":1786320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Nose-to-brain delivery offers a noninvasive route to bypass the blood\u2013brain barrier for the treatment of neurodegenerative diseases. AmyP53 is a first-in-class adaptive 12-mer peptide that prevents the formation of neurotoxic amyloid oligomers by competitively targeting lipid raft gangliosides on brain cell membranes, thereby blocking the shared pathological mechanism underlying both Alzheimer\u2019s and Parkinson\u2019s diseases. Objective: Here, we report the identification of optimal spray devices for the nose-to-brain delivery of AmyP53, ahead of a planned Phase 1 clinical trial. Method\/Results: Among six devices evaluated (four commercial systems and two novel devices specifically engineered for nose-to-brain delivery), two systems were identified as optimal for further clinical development (narrower plume angles and significantly higher deposition in the olfactory region): the Neurospray\u2122 and Neurospray\u2122 Preservative-Free (PF). AmyP53 was quantitatively and reproducibly delivered by both Neurospray\u2122 systems, retaining full recognition of its therapeutic target (gangliosides), as assessed by a surface pressure-based ganglioside-binding assay. In a rabbit preclinical model, intranasal administration of AmyP53 with the Neurospray\u2122 resulted in rapid and sustained brain delivery, detectable at 10 min and persisting at 24 h post-administration, without significant systemic exposure. Conclusions: These results validate the Neurospray\u2122 drug delivery systems as optimal drug delivery systems for the clinical development of AmyP53.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080987","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T15:10:24Z","timestamp":1786374624000},"page":"987","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Optimal Spray Device for the Nose-to-Brain Delivery of AmyP53, an Adaptive Therapeutic Peptide for Alzheimer\u2019s and Parkinson\u2019s Diseases"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9717-4565","authenticated-orcid":false,"given":"Gon\u00e7alo","family":"Farias","sequence":"first","affiliation":[{"name":"Aptar Pharma, 27100 Le Vaudreuil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Chahinian","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine, Aix-Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Hauchard","sequence":"additional","affiliation":[{"name":"Aptar Pharma, 27100 Le Vaudreuil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Brunet","sequence":"additional","affiliation":[{"name":"Aptar Pharma, 27100 Le Vaudreuil, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8653-5521","authenticated-orcid":false,"given":"Jacques","family":"Fantini","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine, Aix-Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2800-5458","authenticated-orcid":false,"given":"Nouara","family":"Yahi","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Medicine, Aix-Marseille University, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Driss","family":"Fantini","sequence":"additional","affiliation":[{"name":"AmyPore, 13240 Sept\u00e8mes-les-Vallons, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4865-724X","authenticated-orcid":false,"given":"Ana\u00efs","family":"Aulas","sequence":"additional","affiliation":[{"name":"AmyPore, 13240 Sept\u00e8mes-les-Vallons, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"ref_1","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. 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