{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:01:00Z","timestamp":1792803660293,"version":"4.5.0"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Youth Science and Technology Fund Program of Gansu province","award":["26JRRA379"],"award-info":[{"award-number":["26JRRA379"]}]},{"name":"Lanzhou Youth Science and Technology Talent Innovation Project","award":["2024-QN-141"],"award-info":[{"award-number":["2024-QN-141"]}]},{"name":"Key Research and Development Program of Gansu Province","award":["24YFNA017"],"award-info":[{"award-number":["24YFNA017"]}]},{"name":"Research-Industry Integration and Key Technology Empowerment Program of Gansu Province","award":["25FNNA001"],"award-info":[{"award-number":["25FNNA001"]}]},{"name":"Ministry of Agriculture and Rural Affairs of the People\u2019s Republic of China-National Beef Cattle Industrial Technology System","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}],"id":[{"id":"https:\/\/ror.org\/05b2wbh21","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Innovation Project of the Chinese Academy of Agricultural Sciences","award":["CAAS-ASTIP-2014-LIHPS"],"award-info":[{"award-number":["CAAS-ASTIP-2014-LIHPS"]}],"id":[{"id":"https:\/\/ror.org\/0313jb750","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Objective: The therapeutic efficacy of the classic antibiotic combination trimethoprim\/sulfamethoxazole (TMP\/SMZ) is often limited by the significant pharmacokinetic mismatch. In this study, a polyethylene glycol-polylactic-co-glycolic acid (PEG-PLGA) nanodelivery system was employed to improve the pharmacokinetic matching of TMP and SMZ. The investigation also evaluated the enhanced in vivo antibacterial efficacy of this formulation. Methods: Ultra-High Performance Liquid Chromatography\u2013Tandem Mass Spectrometry (UPLC-MS\/MS) was employed to systematically characterize the absorption, distribution, and excretion profiles of PEG-PLGA-loaded TMP nanoparticles (NPs) in rats. In vitro antibacterial activity was assessed against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo efficacy and biosafety of the TMP NPs\/SMZ regimen were evaluated using a murine E. coli infection model via survival monitoring, biochemical assays, and histopathology. Results: Pharmacokinetic analysis revealed that TMP NPs achieved a relative bioavailability of 193.05% and extended the elimination half-life by 3.37-fold compared to free TMP. Tissue distribution showed significantly increased drug accumulation in the liver, spleen, and kidneys, with renal clearance as the primary excretion pathway (73.89%). In vitro, the nano-formulation reduced the minimum inhibitory concentration (MIC) by 2-4-fold and shortened the bactericidal duration from 12 to 8 h. In vivo, the TMP NPs\/SMZ combination significantly improved survival rates, accelerated recovery, and alleviated infection-induced organ damage without systemic toxicity. Conclusions: This nanotechnology-based strategy effectively aligns the pharmacokinetics of TMP and SMZ, prolongs their synergistic window, and enhances biosafety, offering a viable approach to revitalize classic antibiotic combinations.<\/jats:p>","DOI":"10.3390\/antibiotics15030283","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T14:45:39Z","timestamp":1773153939000},"page":"283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Revitalizing Trimethoprim\/Sulfamethoxazole via Nanotechnology for Improved Pharmacokinetics and Antibacterial Efficacy"],"prefix":"10.3390","volume":"15","author":[{"given":"Yaxin","family":"Zhou","sequence":"first","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"College of Veterinary Medicine, Northwest Agriculture & Forestry University, Yangling 712100, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guonian","family":"Dai","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Li","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6378-2527","authenticated-orcid":false,"given":"Bintao","family":"Zhai","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulin","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest Agriculture & Forestry University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China"},{"name":"Key Laboratory of New Animal Drug Project of Gansu Province, Lanzhou 730050, China"},{"name":"Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou 730050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1128\/AAC.39.2.279","article-title":"Trimethoprim and Sulfonamide Resistance","volume":"39","author":"Huovinen","year":"1995","journal-title":"Antimicrob. 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