{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T19:43:24Z","timestamp":1784317404288,"version":"3.55.0"},"reference-count":79,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science","award":["BR24992760-OT-24"],"award-info":[{"award-number":["BR24992760-OT-24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Our work was designed to study the physicochemical properties, safety profile, pharmacokinetics, and prophylactic efficacy of an original iodine\u2013dextrin-based pharmaceutical formulation (PA), both alone and in combination with azithromycin (AZ), in a murine model of LPS-induced sepsis. Methods\/Results: UV\u2013vis and 1H-NMR spectroscopy confirmed the formation of a stable iodine\u2013dextrin complex, with triiodide anions stabilized by hydrogen bonding and donor\u2013acceptor interactions. No clinical signs of acute toxicity were observed at doses up to 5000 mg\/kg, and subacute administration (62.5 and 125 mg\/kg) showed no adverse effects on hematological or biochemical parameters. A mild, non-pathological enlargement of thyrocytes and parallel increases in TSH, T3, and T4 levels were observed at 125 mg\/kg, consistent with physiological adaptation to iodine. Pharmacokinetic analysis revealed high oral bioavailability (~92%), prolonged half-life (~21 h), and wide tissue distribution with low clearance. In the sepsis model, pretreatment with AZ+PA alleviated clinical symptoms, maintained body weight, and significantly improved hematological parameters, reducing WBCs and CRP levels. The combination also decreased plasma IL-6 and TNF-\u03b1 concentrations more effectively than either agent alone, indicating a synergistic anti-inflammatory effect. Histological analysis confirmed that PA, particularly in combination with AZ, mitigated LPS-induced tissue injury in the liver, kidney, and lungs. Conclusions: These findings suggest that PA is a safe, bioavailable compound with immunomodulatory properties that enhance azithromycin\u2019s protective effects during systemic inflammation. This supports its potential use as a prophylactic agent in clinical settings, such as preoperative immune modulation to prevent sepsis-related complications.<\/jats:p>","DOI":"10.3390\/pharmaceutics17081040","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:02:09Z","timestamp":1754910129000},"page":"1040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Iodine\u2013Dextrin Complex Exhibits No Acute or Subacute Toxicity and Enhances Azithromycin Efficacy in an LPS-Induced Sepsis Model"],"prefix":"10.3390","volume":"17","author":[{"given":"Nailya","family":"Ibragimova","sequence":"first","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7552-0260","authenticated-orcid":false,"given":"Arailym","family":"Aitynova","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9621-3534","authenticated-orcid":false,"given":"Seitzhan","family":"Turganbay","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Lyu","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Ilin","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Vassilyeva","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Issayeva","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamari","family":"Gapurkhaeva","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiy","family":"Krasnoshtanov","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Ponomareva","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Azembayev","sequence":"additional","affiliation":[{"name":"JSC Scientific Center for Anti-Infectious Drugs, Almaty 050060, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/s41579-019-0293-3","article-title":"Antibiotic development\u2014Economic, regulatory and societal challenges","volume":"18","author":"Ardal","year":"2020","journal-title":"Nat. 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