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cells (LSECs) for preserving liver function in chronic liver disease (CLD). Polymeric micelles (PMs) were functionalized by coupling peptide ligands of LSEC membrane receptors CD32b, CD36 and ITGB3. Functionalization was confirmed via spectroscopy and electron microscopy. In vitro and in vivo FPM-Sim internalization was assessed by means of flow cytometry in LSECs, hepatocytes, Kupffer and hepatic stellate cells from healthy rats. Maximum tolerated dose assays were performed in healthy mice and efficacy studies of FPM-Sim were carried out in bile duct ligation (BDL) and thioacetamide (TAA) induction rat models of cirrhosis. Functionalization with the three peptide ligands resulted in stable formulations with a greater degree of in vivo internalization in LSECs than non-functionalized PMs. Administration of FPM-Sim in BDL rats reduced toxicity relative to free simvastatin, albeit with a moderate portal-pressure-lowering effect. In a less severe model of TAA-induced cirrhosis, treatment with FPM-CD32b-Sim nanoparticles for two weeks significantly decreased portal pressure, which was associated with a reduction in liver fibrosis, lower collagen expression as well as the stimulation of nitric oxide synthesis. In conclusion, CD32b-FPM stands out as a good nanotransporter for drug delivery, targeting LSECs, key inducers of liver injury.<\/jats:p>","DOI":"10.3390\/pharmaceutics15102463","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:38:42Z","timestamp":1697294322000},"page":"2463","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Optimization of Statin-Loaded Delivery Nanoparticles for Treating Chronic Liver Diseases by Targeting Liver Sinusoidal Endothelial Cells"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9118-2940","authenticated-orcid":false,"given":"Mar","family":"Gil","sequence":"first","affiliation":[{"name":"Liver Disease Group, Liver Unit, Vall d\u2019Hebron Research Institute (VHIR), Vall d\u2019Hebron University Hospital, Vall d\u2019Hebron Hospital Campus, Universitat Auton\u00f2ma de Barcelona (UAB), 08035 Barcelona, 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Rev. Gastroenterol. Hepatol."},{"key":"ref_5","first-page":"7","article-title":"How to face chronic liver disease: The sinusoidal perspective","volume":"10","year":"2017","journal-title":"Front. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2016.07.009","article-title":"Liver sinusoidal endothelial cells: Physiology and role in liver diseases","volume":"66","author":"Poisson","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/alcalc\/28.Supplement_1B.77","article-title":"Studies on capillarization of the hepatic sinusoids in alcoholic liver disease","volume":"1","author":"Urashima","year":"1993","journal-title":"Alcohol. Suppl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1016\/S0002-9440(10)63487-6","article-title":"Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis","volume":"163","author":"Xu","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1080\/17425255.2020.1801634","article-title":"An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins","volume":"16","author":"Hirota","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1124\/pr.111.004994","article-title":"Pharmacological actions of statins: A critical appraisal in the management of cancer","volume":"64","author":"Gazzerro","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1136\/gut.2010.220913","article-title":"Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver","volume":"60","author":"Russo","year":"2011","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1136\/gutjnl-2014-308338","article-title":"KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: Behind the molecular mechanisms of statins","volume":"64","author":"Marrone","year":"2015","journal-title":"Gut"},{"key":"ref_13","first-page":"7","article-title":"A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats","volume":"13","author":"Raurell","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1136\/gutjnl-2014-308800","article-title":"Statins, Rho GTPases and KLF2: New mechanistic insight into liver fibrosis and portal hypertension","volume":"64","author":"Trebicka","year":"2015","journal-title":"Gut"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.3748\/wjg.v27.i28.4639","article-title":"Addition of statins to the standard treatment in patients with cirrhosis: Safety and efficacy","volume":"27","author":"Pollarsky","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12876-021-01704-w","article-title":"A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis","volume":"21","author":"Sung","year":"2021","journal-title":"BMC Gastroenterol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1053\/j.gastro.2016.01.004","article-title":"Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients with Cirrhosis","volume":"150","author":"Abraldes","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102267","DOI":"10.1016\/j.nano.2020.102267","article-title":"Simvastatin-loaded polymeric micelles are more effective and less toxic than conventional statins in a pre-clinical model of advanced chronic liver disease","volume":"29","author":"Hide","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0169-409X(01)00222-8","article-title":"Advanced drug delivery devices via self-assembly of amphiphilic block copolymers","volume":"53","author":"Rosler","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jconrel.2021.01.022","article-title":"Polymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo","volume":"331","author":"Andrade","year":"2021","journal-title":"J. Control Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"757469","DOI":"10.3389\/fphys.2021.757469","article-title":"The Scavenger Function of Liver Sinusoidal Endothelial Cells in Health and Disease","volume":"12","author":"Bhandari","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"86","DOI":"10.2174\/978160805293611201010086","article-title":"Pharmacological Effects of Estrogen in Liver Cirrhosis-Induced Portal Hypertension","volume":"Volume 1","author":"Ueno","year":"2012","journal-title":"Preventive Female Sex Factors against the Development of Chronic Liver Disease"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2712","DOI":"10.4049\/jimmunol.165.5.2712","article-title":"Simvastatin Modulates Cytokine-Mediated Endothelial Cell Adhesion Molecule Induction: Involvement of an Inhibitory G Protein","volume":"165","author":"Sadeghi","year":"2000","journal-title":"J. Immunology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/cpch.61","article-title":"Native Chemical Ligation of Peptides and Proteins","volume":"11","author":"Cistrone","year":"2019","journal-title":"Curr. Protoc. Chem. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1080\/10717544.2018.1461276","article-title":"AKT2 siRNA delivery with amphiphilic-based polymeric micelles show efficacy against cancer stem cells","volume":"25","author":"Rafael","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.jhep.2007.03.014","article-title":"Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers","volume":"47","author":"Bosch","year":"2007","journal-title":"J. Hepatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1152\/ajpgi.00300.2004","article-title":"Sinusoidal endothelial COX-1-derived prostanoids modulate the hepatic vascular tone of cirrhotic rat livers","volume":"288","author":"Graupera","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 Years of Image Analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1038\/s41575-020-00411-3","article-title":"Role of liver sinusoidal endothelial cells in liver diseases","volume":"18","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1111\/jphp.13147","article-title":"Influence of PEGylation on PLGA nanoparticle properties, hydrophobic drug release and interactions with human serum albumin","volume":"71","author":"Samkange","year":"2019","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jconrel.2014.10.001","article-title":"Cytotoxicity and internalization of Pluronic micelles stabilized by core cross-linking","volume":"196","author":"Arranja","year":"2014","journal-title":"J. Control Release"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4350","DOI":"10.1021\/la304836e","article-title":"Encapsulation of hydrophobic drugs in pluronic F127 micelles: Effects of drug hydrophobicity, solution temperature, and pH","volume":"29","author":"Basak","year":"2013","journal-title":"Langmuir"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20183","DOI":"10.1038\/s41598-019-56366-2","article-title":"Restoration of liver sinusoidal cell phenotypes by statins improves portal hypertension and histology in rats with NASH","volume":"9","author":"Bravo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12944-018-0790-9","article-title":"Long-chain fatty acid activates hepatocytes through CD36 mediated oxidative stress","volume":"17","author":"Liu","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1002\/hep.23144","article-title":"Pharmacological inhibition of integrin \u03b1v\u03b23 aggravates experimental liver fibrosis and suppresses hepatic angiogenesis","volume":"50","author":"Patsenker","year":"2009","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1055\/s-0037-1617455","article-title":"Liver Sinusoidal Endothelial Cell: An Update","volume":"37","author":"DeLeve","year":"2017","journal-title":"Semin Liver Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/S0016-5085(81)80009-1","article-title":"Clearance Capacity of Rat Liver Kupffer, Endothelial, and Parenchymal Cells","volume":"81","author":"Brouwer","year":"1981","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1189\/jlb.4VMLT0215-054R","article-title":"The liver sinusoidal endothelium reappears after being eclipsed by the Kupffer cell: A 20th century biological delusion corrected","volume":"98","author":"Anderson","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.atherosclerosis.2005.12.025","article-title":"Hyperlipidemia and surfactants: The liver sieve is a link","volume":"189","author":"Cogger","year":"2006","journal-title":"Atherosclerosis"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.bbadis.2017.06.027","article-title":"Animal models of biliary injury and altered bile acid metabolism","volume":"1864","author":"Mariotti","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.bbadis.2018.07.018","article-title":"Animal models of portal hypertension","volume":"1865","author":"Brusilovskaya","year":"2019","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jhep.2021.01.002","article-title":"Pathophysiology of decompensated cirrhosis: Portal hypertension, circulatory dysfunction, inflammation, metabolism and mitochondrial dysfunction","volume":"75","author":"Engelmann","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1089\/ars.2013.5430","article-title":"Statins as regulators of redox state in the vascular endothelium: Beyond lipid lowering","volume":"20","author":"Margaritis","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e76538","DOI":"10.1371\/journal.pone.0076538","article-title":"Simvastatin Ameliorates Liver Fibrosis via Mediating Nitric Oxide Synthase in Rats with Non-Alcoholic Steatohepatitis-Related Liver Fibrosis","volume":"8","author":"Wang","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gil, M., Azkargorta, M., Fuster, C., Mart\u00ednez-G\u00f3mez, M., Raurell, I., Barber\u00e1, A., Peric\u00e0s, J.M., Hide, D., Elortza, F., and Genesc\u00e0, J. (2023). Proteomic Analysis of Dysfunctional Liver Sinusoidal Endothelial Cells Reveals Substantial Differences in Most Common Experimental Models of Chronic Liver Diseases. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241511904"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/10\/2463\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:06:46Z","timestamp":1760130406000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/10\/2463"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,14]]},"references-count":45,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["pharmaceutics15102463"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15102463","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,14]]}}}