{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:33:28Z","timestamp":1790699608180,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"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>Progesterone is a sex hormone which shows neuroprotective effects in different neurodegenerative disorders, including Parkinson\u2019s disease, stroke, and Alzheimer\u2019s disease. However, the pharmacokinetic limitations associated with the peripheral administration of this molecule highlight the need for more efficient delivery approaches to increase brain progesterone levels. Since the nose-to-brain administration of mucoadhesive hydrogel nanoparticles is a non-invasive and convenient strategy for the delivery of therapeutics to the central nervous system, in this work, progesterone-loaded hydrogel nanoparticle formulations have been prepared, characterized, and tested in vivo. Nanoparticles, loaded with different progesterone concentrations, have been obtained by polyelectrolyte complex formation between trimethyl chitosan and sodium alginate, followed by ionotropic gelation with sodium tripolyphosphate as a cross-linking agent. All formulations showed a mean diameter ranging from 200 nm to 236 nm, a polydispersity index smaller than 0.23, and a high progesterone encapsulation efficiency (83\u201395%). The zeta potential values were all positive and greater than 28 mV, thus ensuring nanoparticles stability against aggregation phenomena as well as interaction with negative sialic residues of the nasal mucosa. Finally, in vivo studies on Sprague\u2013Dawley male rats demonstrated a 5-fold increase in brain progesterone concentrations compared to basal progesterone level after 30 min of hydrogel nanoparticle inhalation.<\/jats:p>","DOI":"10.3390\/pharmaceutics11120657","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T10:41:44Z","timestamp":1575628904000},"page":"657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Trimethyl Chitosan Hydrogel Nanoparticles for Progesterone Delivery in Neurodegenerative Disorders"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2788-7823","authenticated-orcid":false,"given":"Maria Cristina","family":"Cardia","sequence":"first","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rosa","family":"Carta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2448-3767","authenticated-orcid":false,"given":"Pierluigi","family":"Caboni","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Maccioni","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Erb\u00ec","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Boi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Meloni","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Sinico","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Unit of Drug Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.neuropharm.2018.04.005","article-title":"Repurposing sex steroids and related drugs as potential treatment for Parkinson\u2019s disease","volume":"147","author":"Bourque","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Vegeto, E., Villa, A., Della Torre, S., Crippa, V., Rusmini, P., Cristofani, R., Galbiati, M., Maggi, A., and Poletti, A. 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