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Interleukin\u20101 receptor antagonist (IL\u20101Ra), a competitive inhibitor of the IL\u20101 receptor, downregulates inflammatory pathways contributing to \u03b2\u2010cell destruction. However, its short half\u2010life (4\u20136\u00a0h) and rapid clearance hinder its clinical effectiveness. In this study, a dual\u2010polymeric system comprising cationic and lipid\u2010based polymers is developed for IL\u20101Ra delivery. IL\u20101Ra nanocomplexes (IL\u20101Ra NCs) are formed through electrostatic interactions, confirmed by SDS\u2010PAGE, TEM, and particle size analysis (167.57\u00a0\u00b1\u00a01.08\u00a0nm for IL\u20101Ra NCs vs 153.21\u00a0\u00b1\u00a01.85\u00a0nm for blank NCs) with zeta potentials of +8.66\u00a0\u00b1\u00a00.46\u00a0mV versus +24.03\u00a0\u00b1\u00a01.1\u00a0mV. In vitro, IL\u20101Ra NCs demonstrate anti\u2010inflammatory activity against IL\u20101\u03b2\u2010induced inflammation in cells. In vivo pharmacokinetic studies show significant improvements in <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>, AUC, half\u2010life (t<jats:sub>1\/2<\/jats:sub>), and mean residence time (MRT) for IL\u20101Ra NCs compared to free IL\u20101Ra, suggesting reduced dosing frequency and enhanced patient compliance. Mice treated with IL\u20101Ra NCs exhibit a significant reduction in fasting blood glucose levels (232.25\u00a0\u00b1\u00a023.64\u00a0mg\u00a0dL<jats:sup>\u22121<\/jats:sup> vs 367.88\u00a0\u00b1\u00a021.83\u00a0mg\u00a0dL<jats:sup>\u22121<\/jats:sup> in the diabetic control). Furthermore, IL\u20101Ra NCs preserve \u03b2\u2010cell integrity and exhibit an improved anti\u2010inflammatory response as assessed by H&amp;E and IHC analysis.<\/jats:p>","DOI":"10.1002\/adhm.202405167","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T11:31:45Z","timestamp":1749468705000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Improved Pharmacokinetic Performance and Pharmacodynamic Efficacy of IL\u20101Ra Complexed with Dual Polymeric Carrier in Type 1 Diabetes Mellitus"],"prefix":"10.1002","volume":"14","author":[{"given":"Shubham A.","family":"Salunkhe","sequence":"first","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science (BITS Pilani)  Pilani Rajasthan 333031 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kommera Sai","family":"Pradyuth","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science (BITS Pilani)  Pilani Rajasthan 333031 India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3344-9579","authenticated-orcid":false,"given":"Anupama","family":"Mittal","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Birla Institute of Technology and Science (BITS Pilani)  Pilani Rajasthan 333031 India"},{"name":"Department of Pharmaceutics National Institute of Pharmaceutical Education and Research (NIPER)  SAS Nagar Punjab 160062 India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-020-0278-5"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-022-00690-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.271"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132612"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nutd.2015.30"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065213"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14163422"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3402"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2017.0035"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2014.07.004"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.04.051"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.59.suppl_1.i60"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2013.04.023"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2006.07.022"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2015.11.015"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.05.061"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.10.012"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2004.09.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920106777950852"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00396-009-2131-z"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213484"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055925"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2025.214284"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cjoc.202000519"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0543"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-013-9642-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27095"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.2001.6285"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vascn.2020.106914"},{"key":"e_1_2_9_30_1","first-page":"13","volume":"9","author":"Lim D. 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