{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:12:32Z","timestamp":1767211952746,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,31]],"date-time":"2023-12-31T00:00:00Z","timestamp":1703980800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FONDECYT","award":["1200109","1201899"],"award-info":[{"award-number":["1200109","1201899"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Polymers"],"abstract":"<jats:p>Iron deficiency anemia (IDA) presents a global health challenge, impacting crucial development stages in humans and other mammals. Pigs, having physiological and metabolic similarities with humans, are a valuable model for studying and preventing anemia. Commonly, a commercial iron dextran formulation (CIDF) with iron dextran particles (IDPs) is intramuscularly administered for IDA prevention in pigs, yet its rapid metabolism limits preventive efficacy. This study aimed to develop and evaluate chitosan thermosensitive hydrogels (CTHs) as a novel parenteral iron supplementation strategy, promoting IDPs\u2019 prolonged release and mitigating their rapid metabolism. These CTHs, loaded with IDPs (0.1, 0.2, and 0.4 g of theoretical iron\/g of chitosan), were characterized for IM iron supplementation. Exhibiting thermosensitivity, these formulations facilitated IM injection at ~4 \u00b0C, and its significant increasing viscosity at 25\u201337 \u00b0C physically entrapped the IDPs within the chitosan\u2019s hydrophobic gel without chemical bonding. In vitro studies showed CIDF released all the iron in 6 h, while CTH0.4 had a 40% release in 72 h, mainly through Fickian diffusion. The controlled release of CTHs was attributed to the physical entrapment of IDPs within the CTHs\u2019 gel, which acts as a diffusion barrier. CTHs would be an effective hydrogel prototype for prolonged-release parenteral iron supplementation.<\/jats:p>","DOI":"10.3390\/polym16010139","type":"journal-article","created":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T13:02:58Z","timestamp":1704114178000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Thermosensitive Chitosan Hydrogels: A Potential Strategy for Prolonged Iron Dextran Parenteral Supplementation"],"prefix":"10.3390","volume":"16","author":[{"given":"Emerson","family":"Dur\u00e1n","sequence":"first","affiliation":[{"name":"Departamento de Fomento de la Producci\u00f3n Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana 8820808, Santiago, Chile"},{"name":"Programa de Doctorado en Ciencias Silvoagropecuarias y Veterinarias, Campus Sur Universidad de Chile, Santa Rosa 11.315, La Pintana 8820808, Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-7518","authenticated-orcid":false,"given":"Andr\u00f3nico","family":"Neira-Carrillo","sequence":"additional","affiliation":[{"name":"Laboratorios de Materiales Bio-Relacionados (CIMAT) y S\u00edntesis y Caracterizaci\u00f3n de Pol\u00edmeros Funcionalizados y Biomol\u00e9culas (POLYFORMS), Departamento de Ciencias Biol\u00f3gicas Animales, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana 8820808, Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felipe","family":"Oyarzun-Ampuero","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias y Tecnolog\u00eda Farmac\u00e9uticas, Facultad de Ciencias Qu\u00edmicas y Farmac\u00e9uticas, Universidad de Chile, Santos Dumont 964, Independencia 8380494, Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1627-3452","authenticated-orcid":false,"given":"Carolina","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Departamento de Fomento de la Producci\u00f3n Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santa Rosa 11.735, La Pintana 8820808, Santiago, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJMra1401038","article-title":"Iron-deficiency anemia","volume":"372","author":"Camaschella","year":"2015","journal-title":"N. Eng. J. Med."},{"key":"ref_2","first-page":"830","article-title":"Global, regional, and national prevalence of anemia and its causes in 204 countries and territories, 1990\u20132019","volume":"4","author":"Gardner","year":"2020","journal-title":"Curr. Dev. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.jfca.2011.01.002","article-title":"Determining iron bio-availability with a constant heme iron value","volume":"24","author":"Hall","year":"2011","journal-title":"J. Food Compos. Anal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0140-6736(07)61235-5","article-title":"Nutritional iron deficiency","volume":"370","author":"Zimmermann","year":"2007","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.tifs.2020.02.021","article-title":"Iron deficiency anemia: A comprehensive review on iron absorption, bioavailability and emerging food fortification approaches","volume":"99","author":"Shubham","year":"2020","journal-title":"Trends Food Sci. Tech."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/S1701-2163(15)30259-0","article-title":"The use of parenteral iron therapy for the treatment of postpartum anemia","volume":"37","author":"Nash","year":"2015","journal-title":"J. Obstet. Gyn. Can."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mayocp.2014.10.007","article-title":"The safety of intravenous iron preparations: Systematic review and meta-analysis","volume":"90","author":"Avni","year":"2015","journal-title":"Mayo Clin. Proc."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2754\/avb200776S8S011","article-title":"Intramuscular versus subcutaneous administration of iron dextran in suckling piglets","volume":"76","author":"Svoboda","year":"2007","journal-title":"Acta Vet. Brno"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2527\/jas.2015-9698","article-title":"Characterization of an encapsulated oral iron supplement to prevent iron\u2013deficiency anemia in neonatal piglets","volume":"94","author":"Antileo","year":"2016","journal-title":"J. Anim. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10","DOI":"10.54846\/jshap\/922","article-title":"An investigation of iron deficiency and anemia in piglets and the effect of iron status at weaning on post-weaning performance","volume":"24","author":"Perri","year":"2016","journal-title":"J. Swine Health Prod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/j.seminhematol.2013.03.028","article-title":"Aplastic anemia: What have we learned from animal models and from the clinic","volume":"50","author":"Scheinberg","year":"2013","journal-title":"Semin. Hematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1017\/S1751731113001134","article-title":"Advantages and disadvantages of the animal models v. In vitro studies in iron metabolism: A review","volume":"7","year":"2013","journal-title":"Animal"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1002\/jps.20093","article-title":"The molecular formula and proposed structure of the iron\u2013dextran complex, imferon","volume":"93","author":"London","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"200","DOI":"10.54846\/jshap\/1042","article-title":"Comparison of the pharmacokinetics and efficacy of two different iron supplementation products in suckling piglets","volume":"26","author":"Morales","year":"2018","journal-title":"J. Swine Health Prod."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Starzy\u0144ski, R., Laarakkers, C., Tjalsma, H., Swinkels, D., Pieszka, M., Sty\u015b, A., Mickiewicz, M., and Lipi\u0144ski, P. (2013). Iron supplementation in suckling piglets: How to correct iron deficiency anemia without affecting plasma hepcidin levels. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064022"},{"key":"ref_16","first-page":"350","article-title":"Iron deficiency and overload. Implications in oxidative stress and cardiovascular health","volume":"25","author":"Toxqui","year":"2010","journal-title":"Nutr. Hosp."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2353\/ajpath.2010.091020","article-title":"Benefits and risks of iron supplementation in anemic neonatal pigs","volume":"177","author":"Tudek","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1517\/17425247.2014.867326","article-title":"Thermosensitive chitosan\/glycerophosphate-based hydrogel and its derivatives in pharmaceutical and biomedical applications","volume":"11","author":"Supper","year":"2014","journal-title":"Expert Opin. Drug Del."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.carbpol.2014.09.094","article-title":"Glycerophosphate-based chitosan thermosensitive hydrogels and their biomedical applications","volume":"117","author":"Zhou","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1016\/j.carbpol.2010.10.022","article-title":"Biocompatibility and characteristics of injectable chitosan-based thermosensitive hydrogel for drug delivery","volume":"83","author":"Zhou","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_21","first-page":"100007","article-title":"Chitosan\/\u03b2-glycerophosphate in situ gelling mucoadhesive systems for intravesical delivery of mitomycin-c","volume":"1","author":"Kolawole","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1007\/s10856-011-4386-4","article-title":"The osteogenic differentiation of dog bone marrow mesenchymal stem cells in a thermo-sensitive injectable chitosan\/collagen\/beta-glycerophosphate hydrogel: In vitro and in vivo","volume":"22","author":"Sun","year":"2011","journal-title":"J. Mater. Sci-mater. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24112","DOI":"10.1038\/srep24112","article-title":"Dual-functional transdermal drug delivery system with controllable drug loading based on thermosensitive poloxamer hydrogel for atopic dermatitis treatment","volume":"6","author":"Wang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s00217-012-1705-z","article-title":"Technological and sensory pork quality in relation to muscle and drip loss protein profiles","volume":"234","author":"Przybylski","year":"2012","journal-title":"Eur. Food Res. Technol."},{"key":"ref_25","unstructured":"Groves, M. (2014). Parenteral Products: The Preparation and Quality Control of Products for Injection, Elsevier."},{"key":"ref_26","first-page":"e04701","article-title":"Safety and efficacy of iron dextran as a feed additive for piglets","volume":"15","author":"Rychen","year":"2017","journal-title":"Efsa J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1002\/jps.23429","article-title":"Minimally invasive transdermal delivery of iron\u2013dextran","volume":"102","author":"Juluri","year":"2013","journal-title":"J. Pharm. Sci."},{"key":"ref_28","first-page":"255","article-title":"Effect of zeta potential on the properties of nano-drug delivery systems-a review (part 1)","volume":"12","author":"Honary","year":"2013","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.apsusc.2005.01.027","article-title":"Core-shell structure and magnetic properties of magnetite magnetic fluids stabilized with dextran","volume":"252","author":"Xu","year":"2005","journal-title":"Appl. Surf. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s10971-008-1891-0","article-title":"Effect of organic and inorganic acids on chitosan\/glycerophosphate thermosensitive hydrogel","volume":"50","author":"Zhao","year":"2009","journal-title":"J. Sol-Gel Sci. Technol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1680\/jbibn.15.00022","article-title":"Insight into the interactive effects of \u03b2-glycerophosphate molecules on thermosensitive chitosan-based hydrogels","volume":"5","author":"Rahmati","year":"2016","journal-title":"Bioinspired Biomim. Nanobiomater."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"112229","DOI":"10.1016\/j.eurpolymj.2023.112229","article-title":"Chitosan with enhanced deprotonation for accelerated thermosensitive gelation with \u03b2-glycerophosphate","volume":"196","author":"Liu","year":"2023","journal-title":"Eur. Polym. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1021\/bm700520m","article-title":"Ionization and solubility of chitosan solutions related to thermosensitive chitosan\/glycerol-phosphate systems","volume":"8","author":"Filion","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"46459","DOI":"10.1002\/app.46459","article-title":"The structural (FTIR, XRD, and XPS) and biological studies of thermosensitive chitosan chloride gels with \u03b2-glycerophosphate disodium","volume":"135","author":"Skwarczynska","year":"2018","journal-title":"J. Appl. Polym. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.msec.2017.04.109","article-title":"Enhanced gelation of chitosan\/\u03b2-sodium glycerophosphate thermosensitive hydrogel with sodium bicarbonate and biocompatibility evaluated","volume":"78","author":"Deng","year":"2017","journal-title":"Mater. Sci. Eng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s12034-021-02434-1","article-title":"Characterization and molecular dynamic studies of chitosan\u2013iron complexes","volume":"44","author":"Fahmy","year":"2021","journal-title":"Bull. Mater. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ejpb.2021.05.023","article-title":"The key role of the drug self-aggregation ability to obtain optimal nanocarriers based on aromatic-aromatic drug-polymer interactions","volume":"166","author":"Guerrero","year":"2021","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1208\/s12248-010-9185-1","article-title":"DDSolver: An add-in program for modeling and comparison of drug dissolution profiles","volume":"12","author":"Zhang","year":"2010","journal-title":"AAPS J."}],"container-title":["Polymers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/1\/139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:45:29Z","timestamp":1760132729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4360\/16\/1\/139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,31]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["polym16010139"],"URL":"https:\/\/doi.org\/10.3390\/polym16010139","relation":{},"ISSN":["2073-4360"],"issn-type":[{"type":"electronic","value":"2073-4360"}],"subject":[],"published":{"date-parts":[[2023,12,31]]}}}