{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:37:51Z","timestamp":1788478671539,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>Poloxamer-based drug delivery systems are widely used in the pharmaceutical sector. The structural characterization of these systems is crucial for the development of new drug delivery systems and for the optimization of their properties. In this study, we utilized small-angle neutron scattering (SANS) to investigate the structures of poloxamer-based drug delivery systems. The samples were measured using the SANS technique on the VSANS-V16 instrument at Helmholtz-Zentrum Berlin (HZB), Germany. The samples contained 20% poloxamer (P407) and 0.2% of a drug (ibuprofen, ketoprofen, diclofenac) in deuterated water (D2O) for SANS. The samples varied in terms of temperature analysis (25 \u00b0C, common storage temperature; 37 \u00b0C, human body temperature; 40 \u00b0C, fever temperature). The data analysis involved modeling the data using a Python-based routine. The model used consisted of an isotropic solution of polydisperse spherical micelles. The intensity as a function of the scattering vector was modeled as the product of the form factor and the interparticle structure factor, with the latter described within the local monodisperse approximation regime. Additionally, a scattering contribution was observed, which was associated with the presence of crystalline superstructures formed by micelles that organized into a cubic structure. The data analysis provided important information about the system, such as the average radius, the size distribution, and the thickness of the layer surrounding the micellar core. The results will contribute to the development and optimization of new drug delivery systems that are more effective and safer for medical applications.<\/jats:p>","DOI":"10.3390\/gels11060410","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T06:14:27Z","timestamp":1748585667000},"page":"410","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Poloxamer-Driven Drug Delivery System for Anti-Inflammatory Drugs Using Small-Angle Neutron Scattering Approach"],"prefix":"10.3390","volume":"11","author":[{"given":"Rodrigo","family":"Rhinow","sequence":"first","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Engenharia e Ci\u00eancia dos Materiais, Universidade Federal do Paran\u00e1, Curitiba 81531-980, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5336-7701","authenticated-orcid":false,"given":"Margareth K. K. D.","family":"Franco","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisas Energ\u00e9ticas e Nucleares, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mont Kumpugdee","family":"Vollrath","sequence":"additional","affiliation":[{"name":"Pharmazeutische Technologie, Berliner Hochschule f\u00fcr Technik, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guinther","family":"Kellermann","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Engenharia e Ci\u00eancia dos Materiais, Universidade Federal do Paran\u00e1, Curitiba 81531-980, Brazil"},{"name":"Department of Physics, Universidade Federal do Paran\u00e1, Curitiba 81531-980, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiano","family":"Yokaichiya","sequence":"additional","affiliation":[{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Engenharia e Ci\u00eancia dos Materiais, Universidade Federal do Paran\u00e1, Curitiba 81531-980, Brazil"},{"name":"Department of Physics, Universidade Federal do Paran\u00e1, Curitiba 81531-980, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.actbio.2020.04.028","article-title":"Poloxamer: A versatile tri-block copolymer for biomedical applications","volume":"110","author":"Zarrintaj","year":"2020","journal-title":"Acta Biomater."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bodratti, A.M., and Alexandridis, P. (2018). Formulation of Poloxamers for Drug Delivery. J. Funct. Biomater., 9.","DOI":"10.3390\/jfb9010011"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1021\/acs.chemrev.8b00199","article-title":"Block Copolymer Micelles in Nanomedicine Applications","volume":"118","author":"Cabral","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e21125","DOI":"10.1590\/s2175-97902022e21125","article-title":"Mini-review of poloxamer as a biocompatible polymer for advanced drug delivery","volume":"58","author":"Nugraha","year":"2023","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3109\/03639040903061363","article-title":"Modified drug release of poloxamer matrix by including water-soluble and water-insoluble polymer","volume":"36","author":"Gonzalez","year":"2010","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ijpharm.2010.08.018","article-title":"Poloxamer 407 microspheres for orotransmucosal drug delivery. Part II: In vitro\/in vivo evaluation","volume":"400","author":"Monti","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33952","DOI":"10.1039\/D4RA06253A","article-title":"A doxorubicin loaded chitosan\u2013poloxamer in situ implant for the treatment of breast cancer","volume":"14","author":"Sahoo","year":"2024","journal-title":"RSC Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0049-3848(03)00379-7","article-title":"The mechanism of action of aspirin","volume":"110","author":"Vane","year":"2003","journal-title":"Thrombosis Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.1021\/cr040708m","article-title":"Nonsteroidal anti-inflammatory drugs (NSAIDs): A comparative QSAR study","volume":"105","author":"Michaelidou","year":"2005","journal-title":"Chem. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10787-009-0016-x","article-title":"Ibuprofen: Pharmacology, efficacy, and safety","volume":"17","author":"Rainsford","year":"2009","journal-title":"Inflammopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/S0002-9149(02)02234-8","article-title":"Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: Clinical considerations","volume":"89","author":"FitzGerald","year":"2002","journal-title":"Am. J. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/FPC.0000000000000113","article-title":"PharmGKB summary: Ibuprofen pathways","volume":"25","author":"Mazaleuskaya","year":"2025","journal-title":"Pharmacogenet. Genom."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1080\/03007995.2020.1716703","article-title":"Systematic review of topical diclofenac for the treatment of acute and chronic musculoskeletal pain","volume":"36","author":"Wiffen","year":"2020","journal-title":"Curr. Med. Res. Opin."},{"key":"ref_14","first-page":"172","article-title":"Pain and ketoprofen: What is its role in clinical practice","volume":"62","author":"Atzeni","year":"2010","journal-title":"Reumatismo"},{"key":"ref_15","first-page":"CD001751","article-title":"Nonsteroidal anti-inflammatory drugs for dysmenorrhea","volume":"4","author":"Marjoribanks","year":"2003","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/03639045.2017.1391838","article-title":"Formulation and delivery strategies of ibuprofen: Challenges and opportunities","volume":"44","author":"Irvine","year":"2018","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"91","DOI":"10.18773\/austprescr.2017.037","article-title":"Peptic ulcer disease and non-steroidal anti-inflammatory drugs","volume":"40","author":"Drini","year":"2017","journal-title":"Aust. Prescr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"559","DOI":"10.2174\/1389200218666171108154419","article-title":"Drug-induced nephrotoxicity: Pathogenic mechanisms, biomarkers and prevention strategies","volume":"19","author":"Wu","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1136\/hrt.2005.082388","article-title":"Non-steroidal anti-inflammatory drugs and risk of first hospital admission for heart failure in the general population","volume":"92","author":"Huerta","year":"2006","journal-title":"Heart"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, X., Donnan, P.T., Bell, S., and Guthrie, B. (2017). Non-steroidal anti-inflammatory drug induced acute kidney injury in the community dwelling general population and people with chronic kidney disease: Systematic review and meta-analysis. BMC Nephrol., 18.","DOI":"10.1186\/s12882-017-0673-8"},{"key":"ref_21","first-page":"e1144","article-title":"Cardiovascular risk of nonsteroidal anti-inflammatory drugs: An under-recognized public health issue","volume":"9","author":"Varga","year":"2017","journal-title":"Cureus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1080\/07853890600925843","article-title":"Prevention of anti-inflammatory drug-induced gastrointestinal damage: Benefits and risks of therapeutic strategies","volume":"38","author":"Lanas","year":"2006","journal-title":"Ann. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1159\/000516299","article-title":"In vitro and in vivo evaluation of ibuprofen nanosuspensions for enhanced oral bioavailability","volume":"30","author":"Hedaya","year":"2021","journal-title":"Med. Princ. Pract."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.55544\/jrasb.3.6.6","article-title":"Review on Ketoprofen (Anti-Inflammatory Drug)","volume":"3","author":"Kumar","year":"2024","journal-title":"J. Res. Appl. Sci. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"305","DOI":"10.15171\/apb.2015.043","article-title":"Solid lipid nanoparticles and nanostructured lipid carriers: Structure, preparation and application","volume":"5","author":"Naseri","year":"2015","journal-title":"Adv. Pharm. Bull."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3897\/pharmacia.72.e149517","article-title":"Technological approaches to increase the bioavailability of Ibuprofen","volume":"72","author":"Mihaylov","year":"2025","journal-title":"Pharmacia"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Jamro\u017cy, M., Kud\u0142acik-Kramarczyk, S., Drabczyk, A., and Krzan, M. (2024). Advanced drug carriers: A review of selected protein, polysaccharide, and lipid drug delivery platforms. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020786"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liu, P., Chen, G., and Zhang, J. (2022). A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules, 27.","DOI":"10.3390\/molecules27041372"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Van Alem, C.M.A., Metselaar, J.M., van Kooten, C., and Rotmans, J.I. (2021). Recent advances in liposomal-based anti-inflammatory therapy. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13071004"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15026","DOI":"10.1021\/acs.langmuir.2c01342","article-title":"Small-angle neutron scattering reveals the nanostructure of liposomes with embedded OprF porins of Pseudomonas Aeruginosa","volume":"38","author":"Spinozzi","year":"2022","journal-title":"Langmuir"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"36","DOI":"10.2174\/1570163820666230515162614","article-title":"Small angle Neutron scattering in drug discovery research: A novel tool for advanced study of structures of biological macromolecules","volume":"20","author":"Adhikari","year":"2023","journal-title":"Curr. Drug Discov. Technol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1021\/bm501519u","article-title":"Small angle neutron scattering studies on the internal structure of poly (lactide-co-glycolide)-block-poly (ethylene glycol) nanoparticles as drug delivery vehicles","volume":"16","author":"Yang","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental Algorithms for Scientific Computing in Python","volume":"17","author":"Virtanen","year":"2020","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"Hunter","year":"2007","journal-title":"Comput. Sci. Eng."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"Harris","year":"2020","journal-title":"Nature"},{"key":"ref_36","unstructured":"Guinier, A., and Fournet, G. (1955). Small Angle Scattering of X-Rays, Wiley."},{"key":"ref_37","unstructured":"Jaclsch, S. (2019). Small-Angle Scattering. arXiv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1103\/PhysRevLett.10.321","article-title":"Exact solution of the Percus-Yevick integral equation for hard spheres","volume":"10","author":"Wertheim","year":"1963","journal-title":"Phys. Rev. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1021\/ma00139a013","article-title":"Hard-sphere interactions between spherical domains in diblock copolymers","volume":"17","author":"Kinning","year":"1984","journal-title":"Macromolecules"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1103\/PhysRev.145.83","article-title":"Structure and resistivity of liquid metals","volume":"145","author":"Ashcroft","year":"1966","journal-title":"Phys. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10947","DOI":"10.1063\/1.1479712","article-title":"The liquid\u2013solid transition in a micellar solution of a diblock copolymer in water","volume":"116","author":"Castelletto","year":"2002","journal-title":"J. Chem. Phys."},{"key":"ref_42","first-page":"15610","article-title":"Effect of Acetaminophen on Poloxamer 407 Micelles and Hydrogels: The Relationship between Structural and Physical Properties","volume":"40","author":"Sakuma","year":"2024","journal-title":"Langmuir"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.jcis.2022.10.064","article-title":"Supramolecular structure organization and rheological properties modulate the performance of hyaluronic acid-loaded thermosensitive hydrogels as drug-delivery systems","volume":"630","author":"Sepulveda","year":"2023","journal-title":"J. Colloid Interface Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26424","DOI":"10.1021\/jp066019r","article-title":"Investigation of sol- gel transition in Pluronic F127\/D2O solutions using a combination of small-angle neutron scattering and Monte Carlo simulation","volume":"110","author":"Li","year":"2006","journal-title":"J. Phys. Chem. B"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"114892","DOI":"10.1016\/j.molliq.2020.114892","article-title":"Solubilisation of salicylate in F127 micelles: Effect of pH and temperature on morphology and interactions with cyclodextrin","volume":"322","author":"Valero","year":"2021","journal-title":"J. Mol. Liq."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1107\/S0021889893013810","article-title":"Determination of size distribution from small-angle scattering data for systems with effective hard-sphere interactions","volume":"27","author":"Pedersen","year":"1994","journal-title":"J. Appl. Crystallogr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1021\/ma9512115","article-title":"Scattering form factor of block copolymer micelles","volume":"29","author":"Pedersen","year":"1996","journal-title":"Macromolecules"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1107\/S0021889899012248","article-title":"Form factors of block copolymer micelles with spherical, ellipsoidal and cylindrical cores","volume":"33","author":"Pedersen","year":"2000","journal-title":"J. Appl. Crystallogr."},{"key":"ref_49","unstructured":"Betancourt, T. (2007). Targetable Biodegradable Nanoparticles for Delivery of Chemotherapeutic and Imaging Agents to Ovarian Cancer, The University of Texas at Austin."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1007\/s00464-022-09252-4","article-title":"Novel temperature-responsive hydrogel injected to the incision site for postoperative pain relief in laparoscopic abdominal surgery: A single-blind, randomized, pivotal clinical trial","volume":"36","author":"Choi","year":"2022","journal-title":"Surg. Endosc."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1002\/jbm.820060609","article-title":"Artificial skin I. Preparation and properties of pluronic F-127 gels for treatment of burns","volume":"6","author":"Schmolka","year":"1972","journal-title":"J. Biomed. Mater. Res."}],"container-title":["Gels"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2310-2861\/11\/6\/410\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:43:40Z","timestamp":1760031820000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2310-2861\/11\/6\/410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["gels11060410"],"URL":"https:\/\/doi.org\/10.3390\/gels11060410","relation":{},"ISSN":["2310-2861"],"issn-type":[{"value":"2310-2861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]}}}