{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:12:30Z","timestamp":1788361950283,"version":"build-2803163510"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"21","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2016-02361610"],"award-info":[{"award-number":["RF-2016-02361610"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oxidative stress occurs when physiological antioxidant systems do not manage to counteract the excessive intracellular production of reactive oxygen species (ROS), which accumulate leading to irreversible oxidation of DNA and other biomacromolecules, and thus to the onset of pathological conditions. Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurodegenerative disease characterized by autosomal recessive mutations in the sacsin gene (SACS). It has been demonstrated that cells of ARSACS patients show bioenergetic and mitochondrial impairment, denoted by reduced respiratory chain activities and ATP synthesis. In order to design a suitable therapy for ARSACS, it is essential to consider that treatments need to cross the blood\u2013brain barrier (BBB), a specialized structure that separates the subtle environment of the brain from blood circulation. Nanostructured lipid carriers (NLCs), constituted by a solid lipid shell and a liquid lipid phase in the core, have been fabricated for loading hydrophobic molecules, improving their bioavailability. Idebenone (IDE), a synthetic analogue of coenzyme Q10, is able to inhibit lipid peroxidation and detoxify several free radicals. However, because of its poor solubility, it requires ad hoc drug-delivery systems for enhancing its pharmacokinetic properties, preventing undesired cytotoxicity. In this work, NLCs loaded with idebenone (IDE-NLCs) have been prepared. The nanovectors have been physicochemically characterized, and their biological activity has been evaluated on different central nervous system cell lines. IDE-NLCs demonstrated to be stable in water and in cell culture media, and showed a sustained drug release profile. Interestingly, preliminary data demonstrated their ability to permeate an in vitro BBB model. Their protective antioxidant activity in human healthy primary skin fibroblasts and their therapeutic efficacy in ARSACS-derived primary skin fibroblasts have been also investigated, showing their potential for future development as therapeutic agents.<\/jats:p>","DOI":"10.1021\/acsomega.0c01282","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T18:44:55Z","timestamp":1589481895000},"page":"12451-12466","source":"Crossref","is-referenced-by-count":20,"title":["Development of Nanostructured Lipid Carriers for the\nDelivery of Idebenone in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay"],"prefix":"10.1021","volume":"5","author":[{"given":"Chiara","family":"Martinelli","sequence":"first","affiliation":[{"name":"Istituto Italiano di Tecnologia , , Viale Rinaldo Piaggio 34 , ,","place":["Pontedera, Italy, 56025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia , , Viale Rinaldo Piaggio 34 , ,","place":["Pontedera, Italy, 56025"]},{"name":"Scuola Superiore Sant\u2019Anna , , Viale Rinaldo Piaggio 34 , ,","place":["Pontedera, Italy, 56025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Pucci","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia , , Viale Rinaldo Piaggio 34 , ,","place":["Pontedera, Italy, 56025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gioi","sequence":"additional","affiliation":[{"name":"Politecnico di Torino , , Corso Duca degli Abruzzi 24 , ,","place":["Torino, Italy, 10129"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Caracci","sequence":"additional","affiliation":[{"name":"Politecnico di Torino , , Corso Duca degli Abruzzi 24 , ,","place":["Torino, Italy, 10129"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Macaluso","sequence":"additional","affiliation":[{"name":"Universita\u0300 di Pisa , , Via Luca Ghini 13 , ,","place":["Pisa, Italy, 56126"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Doccini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris , , Via dei Giacinti 3 , Calambrone, ,","place":["Pisa, Italy, 56128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M.","family":"Santorelli","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris , , Via dei Giacinti 3 , Calambrone, ,","place":["Pisa, Italy, 56128"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1192-3647","authenticated-orcid":true,"given":"Gianni","family":"Ciofani","sequence":"additional","affiliation":[{"name":"Istituto Italiano di Tecnologia , , Viale Rinaldo Piaggio 34 , ,","place":["Pontedera, Italy, 56025"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,5,14]]},"reference":[{"key":"2026090210121474100_cit1","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1111\/j.1582-4934.2010.01010.x","article-title":"Basic Mechanisms\nof Neurodegeneration: A Critical Update","volume":"14","author":"Jellinger","year":"2010","journal-title":"J.\nCell. 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Healthcare Mater."},{"key":"2026090210121474100_cit5","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/72769","article-title":"ARSACS, a Spastic Ataxia Common in\nNortheastern Quebec, Is Caused by Mutations in a New Gene Encoding\nan 11.5-Kb ORF","volume":"24","author":"Engert","year":"2000","journal-title":"Nat. Genet."},{"key":"2026090210121474100_cit6","doi-asserted-by":"publisher","first-page":"2755","DOI":"10.1007\/s00415-015-7911-4","article-title":"Powerhouse Failure and Oxidative\nDamage in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay","volume":"262","author":"Criscuolo","year":"2015","journal-title":"J. Neurol."},{"key":"2026090210121474100_cit7","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1073\/pnas.1113166109","article-title":"Mitochondrial Dysfunction and Purkinje Cell Loss in\nAutosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)","volume":"109","author":"Girard","year":"2012","journal-title":"Proc. Natl. Acad. 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