{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T02:56:46Z","timestamp":1773802606463,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science &amp; Technology Major Project \u201cKey New Drug Creation and Manufacturing","award":["2019ZX09201001-003-007"],"award-info":[{"award-number":["2019ZX09201001-003-007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Liver fibrosis is challenging to treat because of the lack of effective agents worldwide. Recently, we have developed a novel compound, N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamido) benzamide referred to as IMB16-4. However, its poor aqueous solubility and poor oral bioavailability obstruct the drug discovery programs. To increase the dissolution, improve the oral bioavailability and enhance the antifibrotic activity of IMB16-4, PVPK30 was selected to establish the IMB16-4 nanoparticles. Drug release behavior, oral bioavailability, and anti-hepatic fibrosis effects of IMB16-4 nanoparticles were evaluated. The results showed that IMB16-4 nanoparticles greatly increased the dissolution rate of IMB16-4. The oral bioavailability of IMB16-4 nanoparticles was improved 26-fold compared with that of pure IMB16-4. In bile duct ligation rats, IMB16-4 nanoparticles significantly repressed hepatic fibrogenesis and improved the liver function. These findings indicate that IMB16-4 nanoparticles will provide information to expand a novel anti-hepatic fibrosis agent.<\/jats:p>","DOI":"10.3390\/ph15010085","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T20:33:04Z","timestamp":1641933184000},"page":"85","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["New IMB16-4 Nanoparticles Improved Oral Bioavailability and Enhanced Anti-Hepatic Fibrosis on Rats"],"prefix":"10.3390","volume":"15","author":[{"given":"Xia","family":"Niu","sequence":"first","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyu","family":"Niu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yucheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9159-091X","authenticated-orcid":false,"given":"Hongwei","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-6286","authenticated-orcid":false,"given":"Guiling","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jconrel.2018.05.021","article-title":"Oral vitamin-A-coupled valsartan nanomedicine: High hepatic stellate cell receptors accessibility and prolonged enterohepatic residence","volume":"283","author":"Shalaby","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1159\/000343852","article-title":"From Cirrhosis to Hepatocellular Carcinoma: New Molecular Insights on Inflammation and Cellular Senescence","volume":"2","author":"Ramakrishna","year":"2013","journal-title":"Liver Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-0036-1597816","article-title":"Regression of Liver Fibrosis","volume":"37","author":"Iredale","year":"2017","journal-title":"Semin. Liver Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"167sr1","DOI":"10.1126\/scitranslmed.3004700","article-title":"Therapy for Fibrotic Diseases: Nearing the Starting Line","volume":"5","author":"Friedman","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrgastro.2011.134","article-title":"Alcoholic liver disease: Pathogenesis and new targets for therapy","volume":"8","author":"Altamirano","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10512","DOI":"10.3748\/wjg.v22.i48.10512","article-title":"Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets","volume":"22","author":"Zhang","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_7","first-page":"36","article-title":"Fibrogenesis, hepatic stellate cells and the immune system","volume":"135","author":"Taimr","year":"2004","journal-title":"Falk Symp."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1111\/j.1440-1746.2006.04658.x","article-title":"Role of hepatic stellate cells in fibrogenesis and the reversal of fibrosis","volume":"22","author":"Kisseleva","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/S0014-2999(99)00418-5","article-title":"Strong antiproliferative effects of baicalein in cultured rat hepatic stellate cells","volume":"378","author":"Inoue","year":"1999","journal-title":"Eur. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1053\/gast.1996.v110.pm8608892","article-title":"Expression of tissue inhibitor of metalloproteinases 1 and 2 is increased in fibrotic human liver","volume":"110","author":"Benyon","year":"1996","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1172\/JCI1018","article-title":"Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors","volume":"102","author":"Iredale","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S8","DOI":"10.1186\/1476-5926-2-S1-S8","article-title":"N-Cadherin cleavage during activated hepatic stellate cell apoptosis is inhibited by tissue inhibitor of metalloproteinase-1","volume":"3","author":"Murphy","year":"2004","journal-title":"Comp. Hepatol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11069","DOI":"10.1074\/jbc.M111490200","article-title":"Inhibition of apoptosis of activated hepatic stellate cells by tissue inhibitor of metalloproteinase-1 is mediated via effects on matrix metalloproteinase inhibition: Implications for reversibility of liver fibrosis","volume":"277","author":"Murphy","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.1111\/j.1440-1746.2007.04961.x","article-title":"Role of adipocytokines in hepatic fibrogenesis","volume":"22","author":"Ikejima","year":"2007","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nature02006","article-title":"Smad-dependent and Smad-independent pathways in TGF-beta family signaling","volume":"425","author":"Derynck","year":"2003","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"ra77","DOI":"10.1126\/scisignal.2004060","article-title":"The p130 isoform of angiomotin is required for Yap-mediated hepatic epithelial cell proliferation and tumorigenesis","volume":"6","author":"Yi","year":"2013","journal-title":"Sci. Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/S2468-1253(16)30110-8","article-title":"Antifibrotics in chronic liver disease: Tractable targets and translational challenges","volume":"1","author":"Ramachandran","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ijpharm.2013.01.019","article-title":"Bottom-up approaches for preparing drug nanocrystals: Formulations and factors affecting particle size","volume":"453","author":"Sinha","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ijpharm.2008.07.023","article-title":"Top-down production of drug nanocrystals: Nanosuspension stabilization, miniaturization and transformation into solid products","volume":"364","author":"Augustijns","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.ijpharm.2007.09.029","article-title":"Effect of arginine hydrochloride and hydroxypropyl cellulose as stabilizers on the physical stability of high drug loading nanosuspensions of a poorly soluble compound","volume":"351","author":"Gupta","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/jphp.12575","article-title":"Preparation and in-vitro\/in-vivo evaluation of curcumin nanosuspension with solubility enhancement","volume":"68","author":"Li","year":"2016","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.jconrel.2013.08.006","article-title":"Stability of nanosuspensions in drug delivery","volume":"172","author":"Wang","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10050","DOI":"10.1039\/D0TB01869D","article-title":"Chemical and physical chitosan hydrogels as prospective carriers for drug delivery: A review","volume":"8","author":"Tian","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.actbio.2020.10.031","article-title":"Advanced materials for drug delivery across mucosal barriers","volume":"119","author":"Bandi","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2174\/187221010792483726","article-title":"Nanoparticles for improved therapeutics and imaging in cancer therapy","volume":"4","author":"Chithrani","year":"2010","journal-title":"Recent Patents Nanotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9219","DOI":"10.1039\/D0NR00810A","article-title":"Vanadium coordination compounds loaded on graphene quantum dots (GQDs) exhibit improved pharmaceutical properties and enhanced anti-diabetic effects","volume":"12","author":"Du","year":"2020","journal-title":"Nanoscale"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6981","DOI":"10.1021\/acs.nanolett.0c01507","article-title":"Magnetothermia-Induced Catalytic Hollow Nanoreactor for Bioorthogonal Organic Synthesis in Living Cells","volume":"20","author":"Lee","year":"2020","journal-title":"Nano Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.matbio.2018.04.006","article-title":"Liver fibrosis: Direct antifibrotic agents and targeted therapies","volume":"68\u201369","author":"Schuppan","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jconrel.2017.06.003","article-title":"Nanosizing techniques for improving bioavailability of drugs","volume":"260","author":"Bansal","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Niu, X., Wang, X., Niu, B., Li, G., Yang, X., Wang, Y., and Li, G. (2021). Novel IMB16-4 Compound Loaded into Silica Nanoparticles Exhibits Enhanced Oral Bioavailability and Increased Anti-Liver Fibrosis In Vitro. Molecules, 26.","DOI":"10.3390\/molecules26061545"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.jconrel.2010.04.029","article-title":"Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan","volume":"145","author":"Zhang","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2015.07.051","article-title":"Development and validation of X-ray diffraction method for quan-titative determination of crystallinity in warfarin sodium products","volume":"493","author":"Siddiqui","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"S502","DOI":"10.1016\/S0016-5085(20)31930-2","article-title":"Sikiric, Pentadecapeptide Bpc 157 Therapy in Bile Duct Ligated (Bdl) Rats. In Rats with Cirrhosis and Portal Hypertension, Bpc 157 May Be Useful Also in the Conditions of the Increased Intracranial Pressure and Vessels Obstruction","volume":"158","author":"Sever","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_34","first-page":"830a","article-title":"Pinealectomy or Prolonged Light Exposure Exacerbates Biliary Proliferation and Senescence and Liver Fibrosis in Bile Duct Ligated (BDL) Rats Via Decreased Biliary Melatonin Synthesis","volume":"68","author":"Chen","year":"2018","journal-title":"Hepatology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3453","DOI":"10.3892\/mmr.2015.3842","article-title":"Inhibition of liver fibrosis using vitamin A-coupled liposomes to deliver matrix metalloproteinase-2 siRNA in vitro","volume":"12","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1111\/bph.13766","article-title":"The anti-hepatic fibrosis effects of dihydrotanshinone I are mediated by disrupting the yes-associated protein and transcriptional enhancer factor D2 complex and stimulating autophagy","volume":"174","author":"Ge","year":"2017","journal-title":"Br. J. Pharmacol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/1\/85\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:14:52Z","timestamp":1760364892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/15\/1\/85"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ph15010085"],"URL":"https:\/\/doi.org\/10.3390\/ph15010085","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,11]]}}}