{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:20:10Z","timestamp":1788142810241,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Laboratory of Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine","award":["04"],"award-info":[{"award-number":["04"]}]},{"award":["04"],"award-info":[{"award-number":["04"]}],"id":[{"id":"https:\/\/ror.org\/024v0gx67","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Innovation Team Project of the Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine","award":["2023CX001"],"award-info":[{"award-number":["2023CX001"]}]},{"name":"Innovation Team Project of the Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine","award":["2024ZZA004"],"award-info":[{"award-number":["2024ZZA004"]}]},{"name":"Project for Enhancing Young and Middle-aged Teacher\u2019s Research Basis Ability in Colleges of Guangxi","award":["2025KY1124"],"award-info":[{"award-number":["2025KY1124"]}]},{"name":"The Young and Middle-aged Teachers\u2019 Basic Research Ability Improvement Project of Universities in Guangxi","award":["2024KY0504"],"award-info":[{"award-number":["2024KY0504"]}]},{"name":"The Natural Science Foundation of Guangxi","award":["2025GXNSFHA069183"],"award-info":[{"award-number":["2025GXNSFHA069183"]}]},{"name":"National Innovation Fund Project of the Center for High-Performance Medical Device Innovation","award":["ZSYIITHT2024-71"],"award-info":[{"award-number":["ZSYIITHT2024-71"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Introduction: Acute lung injury (ALI) is characterized by severe inflammation and oxidative stress. However, effective pharmacological interventions for ALI remain limited. Carnosine, an endogenous dipeptide known for its redox-regulating and immunomodulatory activities, has demonstrated promising protective effects. In the present study, inhalable carnosine-loaded liposomes (Cn-Ls) were developed to enhance pulmonary delivery and achieve localized treatment in a lipopolysaccharide (LPS)-induced ALI model in mice. Methods: Cn-Ls were prepared and systematically evaluated for their morphology, stability, drug-loading capacity, and release kinetics. In vitro assays were performed to evaluate their cytocompatibility, antioxidant activity, and effects on LPS-induced reactive oxygen species (ROS) generation. In an ALI model, inhaled Cn-Ls were administered to assess pulmonary retention and therapeutic efficacy, including lung inflammation, oxidative stress, circulating levels of C-reactive protein (CRP), tumor necrosis factor (TNF)-\u03b1, interleukin (IL)-6, lung architecture, and respiratory function. Results: Encapsulation of carnosine within liposomes markedly prolonged its pulmonary retention (t1\/2 = 1.7 h vs. 1.0 h for free carnosine), providing a more sustained lung-retentive delivery profile for up to 12 h. In vitro assays showed that Cn-Ls had excellent cytocompatibility, reduced cell death, exhibited potent antioxidant activity, and effectively suppressed LPS-induced ROS generation. In an ALI model, inhaled Cn-Ls markedly mitigated lung inflammation and oxidative stress, reduced circulating levels of CRP, TNF-\u03b1, and IL-6, preserved lung architecture, and improved respiratory function. Compared with free carnosine, Cn-Ls exhibited enhanced pulmonary retention and superior therapeutic efficacy. Conclusions: These results identified inhalable Cn-Ls as a potential nanotherapeutic approach for targeted ALI management and provided a foundation for further translational development. However, additional investigations are required to assess the long-term safety of Cn-Ls, optimize formulation stability and scalability, and further elucidate the underlying therapeutic mechanisms before clinical translation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091090","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1090","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effects of Intratracheally Nebulized Carnosine-Loaded Liposomes on Lipopolysaccharide-Induced Acute Lung Injury"],"prefix":"10.3390","volume":"18","author":[{"given":"Chao","family":"Fang","sequence":"first","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daihan","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0552-7735","authenticated-orcid":false,"given":"Jingting","family":"Yin","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiji","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Gan","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Medicine, Tongji University, No. 500 Zhennan Road, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanlei","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Ultrasound in Medicine, Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Huo","sequence":"additional","affiliation":[{"name":"Faculty of Chinese Medicine Science, Guangxi University of Chinese Medicine, No. 13 Wu-he Avenue, Nanning 530222, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, The First Affiliated Hospital of Guilin Medical University, No. 15 Le-qun Road, Guilin 541001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1021\/acscentsci.1c01494","article-title":"A Nanozymatic Solution to Acute Lung Injury","volume":"8","author":"Duan","year":"2021","journal-title":"ACS Cent. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2304304","DOI":"10.1002\/adhm.202304304","article-title":"Efferocytosis-Inspired Biomimetic Nanoplatform for Targeted Acute Lung Injury Therapy","volume":"13","author":"Huang","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"23872","DOI":"10.1021\/acsnano.3c08147","article-title":"Molybdenum Nanodots for Acute Lung Injury Therapy","volume":"17","author":"Yan","year":"2023","journal-title":"ACS Nano"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.apsb.2021.08.009","article-title":"Pulmonary delivery of siRNA against acute lung injury\/acute respiratory distress syndrome","volume":"12","author":"Zoulikha","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e076612","DOI":"10.1136\/bmj-2023-076612","article-title":"Acute respiratory distress syndrome","volume":"387","author":"Wick","year":"2024","journal-title":"BMJ"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1001\/jama.2018.0483","article-title":"Acute Respiratory Distress Syndrome","volume":"319","author":"Stevens","year":"2018","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1001\/jama.2017.18715","article-title":"Association of Broad- vs Narrow-Spectrum Antibiotics with Treatment Failure, Adverse Events, and Quality of Life in Children with Acute Respiratory Tract Infections","volume":"318","author":"Gerber","year":"2017","journal-title":"JAMA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1001\/jamainternmed.2018.1164","article-title":"Inappropriate Use of Steroids for Acute Respiratory Infection","volume":"178","author":"Grady","year":"2018","journal-title":"JAMA Intern. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1111\/all.15997","article-title":"A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce","volume":"79","author":"Milani","year":"2024","journal-title":"Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1001\/jama.2018.0852","article-title":"Procalcitonin Testing to Guide Antibiotic Therapy in Acute Upper and Lower Respiratory Tract Infections","volume":"319","author":"Schuetz","year":"2018","journal-title":"JAMA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2305432","DOI":"10.1002\/advs.202305432","article-title":"Chemical Evolution and Biological Evaluation of Natural Products for Efficient Therapy of Acute Lung Injury","volume":"11","author":"Fan","year":"2023","journal-title":"Adv. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1186\/s12951-024-02615-0","article-title":"Advances in nanomaterial-targeted treatment of acute lung injury after burns","volume":"22","author":"Zhang","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2023.06.018","article-title":"Delivery systems of therapeutic nucleic acids for the treatment of acute lung injury\/acute respiratory distress syndrome","volume":"360","author":"Zhuang","year":"2023","journal-title":"J. Control. Release"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e071004","DOI":"10.1002\/alz.071004","article-title":"Carnosine supplementation improves delayed recall: A systematic review and meta-analysis","volume":"19","author":"Bell","year":"2023","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.redox.2017.08.003","article-title":"Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage","volume":"14","author":"Deng","year":"2018","journal-title":"Redox Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/s41590-023-01719-3","article-title":"Carnosine regulation of intracellular pH homeostasis promotes lysosome-dependent tumor immunoevasion","volume":"25","author":"Yan","year":"2024","journal-title":"Nat. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3175","DOI":"10.1073\/pnas.85.9.3175","article-title":"Antioxidant activity of carnosine, homocarnosine, and anserine present in muscle and brain","volume":"85","author":"Kohen","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Solana-Manrique, C., Sanz, F.J., Mart\u00ednez-Carri\u00f3n, G., and Paricio, N. (2022). Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases. Antioxidants, 11.","DOI":"10.3390\/antiox11050848"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"A336","DOI":"10.1161\/atvb.42.suppl_1.336","article-title":"Abstract 336: Comparing of In-vivo Carnosine Levels in Blood, Urine, and Muscle","volume":"42","author":"Amraotkar","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1007\/BF01948344","article-title":"Carnosine levels in blood","volume":"37","author":"Seely","year":"1981","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e2400509","DOI":"10.1002\/adhm.202400509","article-title":"Inhalable Dry Powders for Lung mRNA Delivery","volume":"13","author":"Gordon","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_22","first-page":"124","article-title":"Inhalation delivery of repurposed drugs for lung cancer: Approaches, benefits and challenges","volume":"340","author":"Kumbhar","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"123004","DOI":"10.1016\/j.biomaterials.2024.123004","article-title":"Redox-activatable inhalable mucoadhesive proteinic nanotherapeutics for targeted treatment of lung cancer","volume":"316","author":"Jeong","year":"2025","journal-title":"Biomaterials"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101942","DOI":"10.1016\/j.nantod.2023.101942","article-title":"Inhaled drug delivery: Past, present, and future","volume":"52","author":"Yue","year":"2023","journal-title":"Nano Today"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.addr.2020.06.022","article-title":"Recent advancements in liposome technology","volume":"156","author":"Filipczak","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.jconrel.2018.09.001","article-title":"Drug nanocrystallisation within liposomes","volume":"288","author":"Li","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.addr.2020.07.002","article-title":"Liposomes: Advancements and innovation in the manufacturing process","volume":"154\u2013155","author":"Shah","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9913","DOI":"10.7150\/thno.46417","article-title":"Inhibition of Pendrin by a small molecule reduces Lipopolysaccharide-induced acute Lung Injury","volume":"10","author":"Lee","year":"2020","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.apsb.2016.02.002","article-title":"Andrographolide sulfonate ameliorates lipopolysaccharide-induced acute lung injury in mice by down-regulating MAPK and NF-\u03baB pathways","volume":"6","author":"Peng","year":"2016","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"101794","DOI":"10.1016\/j.redox.2020.101794","article-title":"RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury","volume":"38","author":"Wang","year":"2021","journal-title":"Redox Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sul, O.-J., and Ra, S.W. (2021). Quercetin Prevents LPS-Induced Oxidative Stress and Inflammation by Modulating NOX2\/ROS\/NF-kB in Lung Epithelial Cells. Molecules, 26.","DOI":"10.3390\/molecules26226949"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e2300545","DOI":"10.1002\/smll.202300545","article-title":"Inhaled Lipid Nanoparticles Alleviate Established Pulmonary Fibrosis","volume":"19","author":"Li","year":"2023","journal-title":"Small"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1039\/D4TB01938E","article-title":"Nebulized inhalation drug delivery: Clinical applications and advancements in research","volume":"13","author":"Yan","year":"2025","journal-title":"J. Mater. Chem. B"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.2174\/0929867326666190712140545","article-title":"Carnosine and Lung Disease","volume":"27","author":"Tanaka","year":"2020","journal-title":"Curr. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.1007\/s13346-025-01861-5","article-title":"Formulation and clinical translation of inhalable nanomedicines for the treatment and prevention of pulmonary infectious diseases","volume":"15","author":"Ahmed","year":"2025","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.drudis.2014.09.020","article-title":"Recent advances in controlled pulmonary drug delivery","volume":"20","author":"Liang","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_37","first-page":"44","article-title":"Inhalation treatment of lung cancer: The influence of composition, size and shape of nanocarriers on their lung accumulation and retention","volume":"11","author":"Garbuzenko","year":"2014","journal-title":"Cancer Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1021\/acsnano.5b00028","article-title":"Overcoming the diffusion barrier of mucus and absorption barrier of epithelium by self-assembled nanoparticles for oral delivery of insulin","volume":"9","author":"Shan","year":"2015","journal-title":"ACS Nano"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, J., Huang, Y., Shen, W., Zeng, Y., Miao, Y., Feng, N., and Ci, T. (2025). Effects of Surface Charge of Inhaled Liposomes on Drug Efficacy and Biocompatibility. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17030329"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1099\/jgv.0.000238","article-title":"Carnosine markedly ameliorates H9N2 swine influenza virus-induced acute lung injury","volume":"96","author":"Xu","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"42813","DOI":"10.1038\/srep42813","article-title":"Preventive Effects of Carnosine on Lipopolysaccharide-induced Lung Injury","volume":"7","author":"Tanaka","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000479879","article-title":"Mechanistic Evaluation of the Protective Effect of Carnosine on Acute Lung Injury in Sepsis Rats","volume":"100","author":"Sun","year":"2017","journal-title":"Pharmacology"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1090\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:11:04Z","timestamp":1788142264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/9\/1090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pharmaceutics18091090"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18091090","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]}}}