{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:47:27Z","timestamp":1789732047921,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canadian Institutes of Health Research","award":["PJT-159730"],"award-info":[{"award-number":["PJT-159730"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deferoxamine (DFO) is a water-soluble iron chelator used pharmacologically for the management of patients with transfusional iron overload. However, DFO is not cell-permeable and has a short plasma half-life, which necessitates lengthy parenteral administration with an infusion pump. We previously reported the synthesis of chitosan (CS) nanoparticles for sustained slow release of DFO. In the present study, we developed solid dispersions and nanoparticles of a carboxymethyl water-soluble chitosan derivative (CMCS) for improved DFO encapsulation and release. CS dispersions and nanoparticles with DFO have been prepared by ironical gelation using sodium triphosphate (TPP) and were examined for comparison purposes. The successful presence of DFO in CMCS polymeric dispersions and nanoparticles was confirmed through FTIR measurements. Furthermore, the formation of CMCS nanoparticles led to inclusion of DFO in an amorphous state, while dispersion of DFO in the polymeric matrix led to a decrease in its crystallinity according to X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results. An in vitro release assay indicated sustained release of DFO from CS and CMCS nanoparticles over 48 h and 24 h, respectively. Application of CMCS-DFO dispersions to murine RAW 264.7 macrophages or human HeLa cervical carcinoma cells triggered cellular responses to iron deficiency. These were exemplified in the induction of the mRNA encoding transferrin receptor 1, the major iron uptake protein, and the suppression of ferritin, the iron storage protein. Our data indicate that CMCS-DFO nanoparticles release bioactive DFO that causes effective iron chelation in cultured cells.<\/jats:p>","DOI":"10.3390\/ijms25020913","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T06:52:14Z","timestamp":1704955934000},"page":"913","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Water-Soluble Chitosan Derivative for the Release of Bioactive Deferoxamine"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9417-3767","authenticated-orcid":false,"given":"Georgia","family":"Michailidou","sequence":"first","affiliation":[{"name":"Laboratory of Polymer and Colors Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada"},{"name":"Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1608-0773","authenticated-orcid":false,"given":"Alexandra","family":"Zamboulis","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Colors Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Karlioti","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Colors Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despoina","family":"Meimaroglou","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Colors Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-0057","authenticated-orcid":false,"given":"Kostas","family":"Pantopoulos","sequence":"additional","affiliation":[{"name":"Department of Medicine, McGill University, Montreal, QC H3T 1E2, Canada"},{"name":"Lady Davis Institute for Medical Research, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8458-4952","authenticated-orcid":false,"given":"Dimitrios N.","family":"Bikiaris","sequence":"additional","affiliation":[{"name":"Laboratory of Polymer and Colors Chemistry and Technology, Department of Chemistry, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3610","DOI":"10.1111\/bcp.15343","article-title":"\u03b2-thalassemia, and the advent of new Interventions beyond Transfusion and Iron chelation","volume":"88","author":"Chauhan","year":"2022","journal-title":"Br. 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