{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:47:38Z","timestamp":1788911258563,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Identification of molecules able to promote neuroprotective mechanisms can represent a promising therapeutic approach to neurodegenerative disorders including Huntington\u2019s disease. Curcumin is an antioxidant and neuroprotective agent, even though its efficacy is limited by its poor absorption, rapid metabolism, systemic elimination, and limited blood\u2013brain barrier (BBB) permeability. Herein, we report on novel biodegradable curcumin-containing nanoparticles to favor the compound delivery and potentially enhance its brain bioavailability. The prepared hyaluronan-based materials able to self-assemble in stable spherical nanoparticles, consist of natural fatty acids chemically conjugated to the natural polysaccharide. The aim of this study is to provide a possible effective delivery system for curcumin with the expectation that, after having released the drug at the specific site, the biopolymer can degrade to nontoxic fragments before renal excretion, since all the starting materials are provided by natural resource. Our findings demonstrate that curcumin-encapsulated nanoparticles enter the cells and reduce their susceptibility to apoptosis in an in vitro model of Huntington\u2019s disease.<\/jats:p>","DOI":"10.3390\/ijms21228846","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T08:18:23Z","timestamp":1606119503000},"page":"8846","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Curcumin-Loaded Nanoparticles Based on Amphiphilic Hyaluronan-Conjugate Explored as Targeting Delivery System for Neurodegenerative Disorders"],"prefix":"10.3390","volume":"21","author":[{"given":"Giuseppe","family":"Pepe","sequence":"first","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Calce","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Verdoliva","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5086-2459","authenticated-orcid":false,"given":"Michele","family":"Saviano","sequence":"additional","affiliation":[{"name":"Institute of Crystallography, National Research Council, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittorio","family":"Maglione","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Di Pardo","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7078-1696","authenticated-orcid":false,"given":"Stefania","family":"De Luca","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging, National Research Council, 80134 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1007\/BF01965935","article-title":"Anti-inflammatory and irritant activities of curcumin analogues in rats","volume":"12","author":"Mukhopadhyay","year":"1982","journal-title":"Agents Actions"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-0-387-46401-5_3","article-title":"Antioxidant and anti-inflammatory properties of curcumin","volume":"595","author":"Menon","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-0-387-46401-5_8","article-title":"Neuroprotective effects of curcumin","volume":"595","author":"Cole","year":"2007","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_4","first-page":"4012","article-title":"Curcumin dietary supplementation ameliorates disease phenotype in an animal model of Huntington\u2019s disease","volume":"28","author":"Elifani","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington\u2019s disease: A clinical review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/mp700113r","article-title":"Bioavailability of curcumin: Problems and promises","volume":"4","author":"Anand","year":"2007","journal-title":"Mol. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.2147\/IJN.S208332","article-title":"Curcumin-loaded nanoparticles: A novel therapeutic strategy in treatment of central nervous system disorders","volume":"14","author":"Pirzadeh","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_8","first-page":"1994","article-title":"Curcumin nanomedicine: A road to cancer therapeutics","volume":"19","author":"Yallapu","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1021\/acs.biomac.5b01019","article-title":"Release-Modulated Antioxidant Activity of a Composite Curcumin-Chitosan Polymer","volume":"17","author":"Soucy","year":"2016","journal-title":"Biomacromolecules"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1208\/s12248-012-9444-4","article-title":"Highly stabilized curcumin nanoparticles tested in an in vitro blood-brain barrier model and in Alzheimer\u2019s disease Tg2576 mice","volume":"15","author":"Cheng","year":"2013","journal-title":"AAPS J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ijpharm.2011.06.030","article-title":"Curcumin and its nano-formulation: The kinetics of tissue distribution and blood\u2013brain barrier penetration","volume":"416","author":"Tsai","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1021\/nn405077y","article-title":"Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in Alzheimer\u2019s disease model via canonical Wnt\/\u03b2-catenin pathway","volume":"8","author":"Tiwari","year":"2014","journal-title":"ACS Nano."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s12017-013-8261-y","article-title":"Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington\u2019s disease","volume":"16","author":"Sandhir","year":"2014","journal-title":"Neuromol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.jddst.2019.05.042","article-title":"In vitro cell uptake evaluation of curcumin-loaded PCL\/F68 nanoparticles for potential application in neuronal diseases","volume":"52","year":"2019","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.carbpol.2016.02.001","article-title":"Eco-friendly microwave-assisted protocol to prepare hyaluronan-fatty acid conjugates and to induce their self-assembly process","volume":"143","author":"Calce","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"29573","DOI":"10.1039\/C5RA03107A","article-title":"A biocompatible process to prepare hyaluronan-based material able to self-assemble into stable nano-particles","volume":"5","author":"Calce","year":"2015","journal-title":"Rsc. Adv."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7181","DOI":"10.1016\/j.biomaterials.2011.06.028","article-title":"Self-assembled nanoparticles based on hyaluronic acid-ceramide (HA-CE) and Pluronic\u00ae for tumor-targeted delivery of docetaxel","volume":"32","author":"Cho","year":"2011","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1523\/JNEUROSCI.6348-09.2010","article-title":"Impaired ganglioside metabolism in Huntington\u2019s disease and neuroprotective role of GM1","volume":"30","author":"Maglione","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3528","DOI":"10.1073\/pnas.1114502109","article-title":"GM1 induces phosphorylation of mutant huntingtin and restores normal motor behavior in Huntington disease mice","volume":"109","author":"Maglione","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5823","DOI":"10.2147\/IJN.S171099","article-title":"Fluorescence properties of curcumin-loaded nanoparticles for cell tracking","volume":"13","author":"Mogharbel","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_21","first-page":"1","article-title":"Novel Insight to Neuroprotective Potential of Curcumin: A Mechanistic Review of Possible Involvement of Mitochondrial Biogenesis and PI3\/Akt\/ GSK3 or PI3\/Akt\/CREB\/BDNF Signaling Pathways","volume":"9","author":"Kandezi","year":"2020","journal-title":"Int. J. Mol. Cell. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1093\/hmg\/ddt615","article-title":"FTY720 (fingolimod) is a neuroprotective and disease-modifying agent in cellular and mouse models of Huntington disease","volume":"23","author":"Amico","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.ejps.2009.02.019","article-title":"Nanoparticles encapsulation improves oral bioavailability of curcumin by at least 9-fold when compared to curcumin administered with piperine as absorption enhancer","volume":"37","author":"Shaikh","year":"2009","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s13318-016-0377-7","article-title":"Enhancement of Curcumin Bioavailability via the Prodrug Approach: Challenges and Prospects","volume":"42","author":"Haworth","year":"2017","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5280","DOI":"10.1038\/s41598-017-05709-y","article-title":"Defective Sphingosine-1-phosphate metabolism is a druggable target in Huntington\u2019s disease","volume":"7","author":"Amico","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3389\/fnmol.2019.00100","article-title":"Stimulation of Sphingosine Kinase 1 (SPHK1) Is Beneficial in a Huntington\u2019s Disease Pre-clinical Model","volume":"12","author":"Pepe","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105009","DOI":"10.1016\/j.nbd.2020.105009","article-title":"Treatment with K6PC-5, a selective stimulator of SPHK1, ameliorates intestinal homeostasis in an animal model of Huntington\u2019s disease","volume":"143","author":"Pepe","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.addr.2007.11.007","article-title":"Clinical toxicities of nanocarrier systems","volume":"60","author":"Takemoto","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2147\/IJN.S38378","article-title":"Nanodrugs: Pharmacokinetics and safety","volume":"20","author":"Onoue","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"10542","DOI":"10.1038\/s41598-017-10836-7","article-title":"Hyaluronic Acid Coated Chitosan Nanoparticles Reduced the Immunogenicity of the Formed Protein Corona","volume":"7","author":"Almalik","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.jconrel.2015.01.030","article-title":"Coating nanocarriers with hyaluronic acid facilitates intravitreal drug delivery for retinal gene therapy","volume":"202","author":"Martens","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.3109\/10717544.2015.1092619","article-title":"Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery","volume":"23","author":"Nasr","year":"2016","journal-title":"Drug Deliv."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8846\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:35:52Z","timestamp":1760178952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/22\/8846"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":32,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21228846"],"URL":"https:\/\/doi.org\/10.3390\/ijms21228846","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]}}}