{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:56:58Z","timestamp":1792540618337,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T00:00:00Z","timestamp":1739750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004951","name":"Atat\u00fcrk University","doi-asserted-by":"publisher","award":["TCD-2022-9606"],"award-info":[{"award-number":["TCD-2022-9606"]}],"id":[{"id":"10.13039\/501100004951","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Over the past 25 years, numerous biological molecules, like recombinant lysosomal enzymes, neurotrophins, receptors, and therapeutic antibodies, have been tested in clinical trials for neurological diseases. However, achieving significant success in clinical applications has remained elusive. A primary challenge has been the inability of these molecules to traverse the blood\u2013brain barrier (BBB). Recognizing this hurdle, our study aimed to utilize niosomes as delivery vehicles, leveraging the \u201cmolecular Trojan horse\u201d technology, to enhance the transport of molecules across the BBB. Methods: Previously synthesized memantine derivatives (MP1\u20134) were encapsulated into niosomes for improved BBB permeability, hypothesizing that this approach could minimize peripheral drug toxicity while ensuring targeted brain delivery. Using the human neuroblastoma (SH-SY5Y) cell line differentiated into neuron-like structures with retinoic acid and then exposed to amyloid beta 1\u201342 peptide, we established an in vitro Alzheimer\u2019s disease (AD) model. In this model, the potential usability of MP1\u20134 was assessed through viability tests (MTT) and toxicological response analysis. The niosomes\u2019 particle size and morphological structures were characterized using scanning electron microscopy (SEM), with their loading and release capacities determined via UV spectroscopy. Crucially, the ability of the niosomes to cross the BBB and their potential anti-Alzheimer efficacy were analyzed in an in vitro transwell system with endothelial cells. Results: The niosomal formulations demonstrated effective drug encapsulation (encapsulation efficiency: 85.3% \u00b1 2.7%), controlled release (72 h release: 38.5% \u00b1 1.2%), and stable morphology (PDI: 0.22 \u00b1 0.03, zeta potential: \u221231.4 \u00b1 1.5 mV). Among the derivatives, MP1, MP2, and MP4 exhibited significant neuroprotective effects, enhancing cell viability by approximately 40% (p &lt; 0.05) in the presence of A\u03b21-42 at a concentration of 47 \u00b5g\/mL. The niosomal delivery system improved BBB permeability by 2.5-fold compared to free drug derivatives, as confirmed using an in vitro bEnd.3 cell model. Conclusions: Memantine-loaded niosomes provide a promising platform for overcoming BBB limitations and enhancing the therapeutic efficacy of Alzheimer\u2019s disease treatments. This study highlights the potential of nanotechnology-based delivery systems in developing targeted therapies for neurodegenerative diseases. Further in vivo studies are warranted to validate these findings and explore clinical applications.<\/jats:p>","DOI":"10.3390\/pharmaceutics17020267","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T07:48:22Z","timestamp":1739778502000},"page":"267","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis and Characterization of Memantine-Loaded Niosomes for Enhanced Alzheimer\u2019s Disease Targeting"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7046-8990","authenticated-orcid":false,"given":"Hasan","family":"Turkez","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Atat\u00fcrk University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sena","family":"Oner","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1412-8411","authenticated-orcid":false,"given":"Ozge Caglar","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1600-2305","authenticated-orcid":false,"given":"Mehmet Enes","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Science, Erzurum Technical University, Erzurum 25100, Turkey"},{"name":"Genescence Biotechnology, Ata Teknokent, Atat\u00fcrk University Technology Development Zone, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-7196","authenticated-orcid":false,"given":"Marilisa Pia","family":"Dimmito","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 6512 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1957-9596","authenticated-orcid":false,"given":"\u00c7igdem Yuce","family":"Kahraman","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Atat\u00fcrk University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8611-6538","authenticated-orcid":false,"given":"Lisa","family":"Marinelli","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 6512 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdal","family":"Sonmez","sequence":"additional","affiliation":[{"name":"Advanced Materials Research Laboratory, Department of Nanoscience & Nanoengineering, Graduate School of Natural and Applied Sciences, Atat\u00fcrk University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"Kiki","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Atat\u00fcrk University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulgani","family":"Tatar","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Atat\u00fcrk University, Erzurum 25100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-0443","authenticated-orcid":false,"given":"Ivana","family":"Cacciatore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 6512 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3042-2234","authenticated-orcid":false,"given":"Antonio","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University \u201cG. D\u2019Annunzio\u201d of Chieti-Pescara, 6512 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Mardinoglu","sequence":"additional","affiliation":[{"name":"Science for Life Laboratory, KTH-Royal Institute of Technology, SE-17121 Stockholm, Sweden"},{"name":"Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King\u2019s College London, London SE1 9RT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sousa, J.A., Bernardes, C., Bernardo-Castro, S., Lino, M., Albino, I., Ferreira, L., Br\u00e1s, J., Guerreiro, R., T\u00e1buas-Pereira, M., and Baldeiras, I. (2023). Reconsidering the Role of Blood-Brain Barrier in Alzheimer\u2019s Disease: From Delivery to Target. Front. 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