{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:06:16Z","timestamp":1782821176124,"version":"3.54.5"},"reference-count":70,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cSMuovilavita Foundation\u201d, NPO, Italy"},{"name":"\u201cAssociazione Sclerosi Tuberosa\u201d, NPO, Italy"},{"name":"\u201cAssociazione Ricerca Alzheimer Lissone ARAL\u201d, NPO, Italy"},{"name":"\u201cNeuroscience Institute of Ros\u00e0\u201d"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A large body of evidence, replicated in many mouse models of Alzheimer\u2019s disease (AD), supports the therapeutic efficacy of the oral mammalian target of rapamycin inhibitors (mTOR-Is). Our preliminary data show that intracerebroventricular (ICV) administration of everolimus (RAD001) soon after clinical onset greatly diminished cognitive impairment and the intracellular beta amyloid and neurofibrillary tangle load. However, RAD001 shows &gt;90% degradation after 7 days in solution at body temperature, thus hampering the development of proper therapeutic regimens for patients. To overcome such a drawback, we developed a stable, liquid formulation of mTOR-Is by loading RAD001 into distearoylphosphatidylethanolamine\u2013polyethylene glycol 2000 (DSPE-PEG2000) micelles using the thin layer evaporation method. The formulation showed efficient encapsulation of RAD001 and a homogeneous colloidal size and stabilised RAD001, with over 95% of activity preserved after 14 days at 37 \u00b0C with a total decay only occurring after 98 days. RAD001-loaded DSPE-PEG2000 micelles were unchanged when stored at 4 and 25 \u00b0C over the time period investigated. The obtained formulation may represent a suitable platform for expedited clinical translation and effective therapeutic regimens in AD and other neurological diseases.<\/jats:p>","DOI":"10.3390\/ijms242417478","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T03:16:33Z","timestamp":1702610193000},"page":"17478","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Stable Micellar Formulation of RAD001 for Intracerebroventricular Delivery and the Treatment of Alzheimer\u2019s Disease and Other Neurological Disorders"],"prefix":"10.3390","volume":"24","author":[{"given":"Laura","family":"Gianessi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-6226","authenticated-orcid":false,"given":"Alessandro","family":"Magini","sequence":"additional","affiliation":[{"name":"Tuberous Sclerosis Association, 00147 Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0280-6238","authenticated-orcid":false,"given":"Roberto","family":"Dominici","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Desio Hospital, ASST-Brianza, 20832 Desio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5043-7233","authenticated-orcid":false,"given":"Stefano","family":"Giovagnoli","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Dolcetta","sequence":"additional","affiliation":[{"name":"Neuroscience Institute of Ros\u00e0, 36027 Ros\u00e0, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"ref_1","first-page":"813","article-title":"Sirolimus and mTOR Inhibitors: A Review of Side Effects and Specific Management in Solid Organ Transplantation","volume":"42","author":"Nguyen","year":"2019","journal-title":"Drug Saf."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0024-3205(95)02233-3","article-title":"Mechanism of Action of the Immunosuppressant Rapamycin","volume":"58","author":"Dumont","year":"1995","journal-title":"Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/S0140-6736(08)61279-9","article-title":"Tuberous Sclerosis","volume":"372","author":"Curatolo","year":"2008","journal-title":"Lancet Lond. 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