{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T21:53:18Z","timestamp":1780609998419,"version":"3.54.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T00:00:00Z","timestamp":1494979200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["AAPS PharmSciTech"],"published-print":{"date-parts":[[2017,11]]},"DOI":"10.1208\/s12249-017-0799-9","type":"journal-article","created":{"date-parts":[[2017,5,17]],"date-time":"2017-05-17T14:56:42Z","timestamp":1495033002000},"page":"3076-3086","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and Hepatoprotective and Toxicity Evaluation"],"prefix":"10.1208","volume":"18","author":[{"given":"Amira E.","family":"El-Nahas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed N.","family":"Allam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa A.","family":"Abdelmonsif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal H.","family":"El-Kamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,17]]},"reference":[{"issue":"4","key":"799_CR1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.4103\/2230-973X.143113","volume":"4","author":"S Gupta","year":"2014","unstructured":"Gupta S, Singh S, Girotra P. Targeting silymarin for improved hepatoprotective activity through chitosan nanoparticles. Int J Pharm Investig. 2014;4(4):156\u201363.","journal-title":"Int J Pharm Investig"},{"issue":"4","key":"799_CR2","first-page":"150","volume":"2","author":"L Liu","year":"2007","unstructured":"Liu L, Pang Z, Zhang W, Wang S. Formulation design and in vitro evaluation of silymarin-loaded self-microemulsifying drug delivery systems. Asian J Pharm Sci. 2007;2(4):150\u201360.","journal-title":"Asian J Pharm Sci"},{"key":"799_CR3","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.ejpb.2005.12.005","volume":"63","author":"W Wu","year":"2006","unstructured":"Wu W, Wang Y, Que L. Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur J Pharm Biopharm. 2006;63:288\u201394.","journal-title":"Eur J Pharm Biopharm"},{"key":"799_CR4","doi-asserted-by":"crossref","unstructured":"Pyszkov\u00e1 M, Biler M, Biedermann D, Valentov\u00e1 K, Kuzma M, Vrba J, et al. Flavonolignan 2,3-dehydroderivatives: preparation, antiradical and cytoprotective activity. Free Rad Bio Med. 2016;90:114\u201325.","DOI":"10.1016\/j.freeradbiomed.2015.11.014"},{"key":"799_CR5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/aps.2010.55","volume":"31","author":"J Yu","year":"2010","unstructured":"Yu J, Zhu Y, Wang L, Peng M, Tong S. Enhancement of oral bioavailability of the poorly water-soluble drug silybin by sodium cholate\/ phospholipid-mixed micelles. Acta Pharmaco Sin. 2010;31:759\u201364.","journal-title":"Acta Pharmaco Sin"},{"issue":"265","key":"799_CR6","first-page":"1","volume":"21","author":"Y Ma","year":"2016","unstructured":"Ma Y, He S, Ma X, Hong T, Li Z, Park K, et al. Silymarin-loaded nanoparticles based on stearic acid-modified Bletilla striata polysaccharide for hepatic targeting. Molecules. 2016;21(265):1\u201310.","journal-title":"Molecules"},{"key":"799_CR7","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1002\/med.20115","volume":"28","author":"A Negi","year":"2008","unstructured":"Negi A, Kumar J, Luqman S, Shanker K, Gupta M, Khanuja S. Recent advances in plant hepatoprotectives: a chemical and biological profile of some important leads. Med Res Rev. 2008;28:746\u201372.","journal-title":"Med Res Rev"},{"key":"799_CR8","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/j.carbpol.2010.09.055","volume":"83","author":"IM El-Sherbiny","year":"2011","unstructured":"El-Sherbiny IM, Abdel-Mogib M, Dawidar MM, Elsayed A, Smyth HD. Biodegradable pH-responsive alginate-poly (lactic-co-glycolic acid) nano\/micro hydrogel matrices for oral delivery of silymarin. Carbohydr Polym. 2011;83:1345\u201354.","journal-title":"Carbohydr Polym"},{"issue":"3","key":"799_CR9","first-page":"239","volume":"16","author":"S Javed","year":"2011","unstructured":"Javed S, Kohli K, Ali M. Reassessing bioavailability of silymarin. Altern Med Rev. 2011;16(3):239\u201349.","journal-title":"Altern Med Rev"},{"key":"799_CR10","first-page":"2403","volume":"10","author":"CH Chen","year":"2015","unstructured":"Chen CH, Chang CC, Shih TH, Aljuffali IA, Yeh TS, Fang JY. Self-nanoemulsifying drug delivery systems ameliorate the oral delivery of silymarin in rats with roux-en-Y gastric bypass surgery. Int J Nanomedicine. 2015;10:2403\u201316.","journal-title":"Int J Nanomedicine"},{"issue":"6","key":"799_CR11","first-page":"672","volume":"21","author":"Y Xie","year":"2016","unstructured":"Xie Y, Yi Y, Hu X, Shangguan M, Wang L, Lu Y, et al. Synchronous microencapsulation of multiple components in silymarin into PLGA nanoparticles by an emulsification\/solvent evaporation method. Pharm Dev Technol. 2016;21(6):672\u20139.","journal-title":"Pharm Dev Technol"},{"key":"799_CR12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biopha.2016.03.042","volume":"81","author":"N Younis","year":"2016","unstructured":"Younis N, Shaheen MA, Abdallah MH. Silymarin-loaded Eudragit RS100 nanoparticles improved the ability of silymarin to resolve hepatic fibrosis in bile duct ligated rats. Biomed Pharmacother. 2016;81:93\u2013103.","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"799_CR13","doi-asserted-by":"crossref","first-page":"4090","DOI":"10.1166\/jnn.2015.9518","volume":"15","author":"SA Guhagarkar","year":"2015","unstructured":"Guhagarkar SA, Shah D, Patel MD, Sathaye SS, Devarajan PV. Polyethylene Sebacate-Silymarin nanoparticles with enhanced Hepatoprotective activity. J Nanosci Nanotechnol. 2015;15(6):4090\u20133.","journal-title":"J Nanosci Nanotechnol"},{"issue":"1\u20132","key":"799_CR14","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ijpharm.2010.07.041","volume":"398","author":"L Plapied","year":"2010","unstructured":"Plapied L, Vandermeulen G, Vroman B, Pr\u00e9at V, des Rieux A. Bioadhesive nanoparticles of fungal chitosan for oral DNA delivery. Int J Pharm. 2010;398(1\u20132):210\u20138.","journal-title":"Int J Pharm"},{"issue":"19","key":"799_CR15","first-page":"1","volume":"9","author":"C Puglia","year":"2016","unstructured":"Puglia C, Lauro MR, Tirendi GG, Fassari GE, Carbone C, Bonina F, et al. Modern drug delivery strategies applied to natural active compounds. Expert Opin Drug Deliv. 2016;9(19):1\u201314.","journal-title":"Expert Opin Drug Deliv"},{"issue":"11","key":"799_CR16","first-page":"2369","volume":"26","author":"SE El-Habashy","year":"2016","unstructured":"El-Habashy SE, Allam AN, El-Kamel AH. Ethyl cellulose nanoparticles as a platform to decrease ulcerogenic potential of piroxicam: formulation and in vitro\/in vivo evaluation. Int J Nanomedicine. 2016;26(11):2369\u201380.","journal-title":"Int J Nanomedicine"},{"issue":"2","key":"799_CR17","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s13204-014-0300-y","volume":"5","author":"UK Sharma","year":"2014","unstructured":"Sharma UK, Verma A, Prajapati SK, Pandey H, Pandey AC. In vitro, in vivo and pharmacokinetic assessment of amikacin sulphate laden polymeric nanoparticles meant for controlled ocular drug delivery. App Nanosci. 2014;5(2):143\u201355.","journal-title":"App Nanosci"},{"key":"799_CR18","first-page":"2429","volume":"6","author":"J Tang","year":"2011","unstructured":"Tang J, Xu N, Ji H, Liu H, Wang Z, Wu L, et al. Eudragit nanoparticles containing genistein: formulation, development, and bioavailability assessment. Int J Nanomedicine. 2011;6:2429\u201335.","journal-title":"Int J Nanomedicine"},{"issue":"4","key":"799_CR19","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s11095-008-9791-0","volume":"26","author":"F-L Yen","year":"2009","unstructured":"Yen F-L, Wu T-H, Lin L-T, Cham T-M, Lin C-C. Naringenin-loaded nanoparticles improve the physicochemical properties and the hepatoprotective effects of naringenin in orally-administered rats with CCl4-induced acute liver failure. Pharm Res. 2009;26(4):893\u2013902.","journal-title":"Pharm Res"},{"key":"799_CR20","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ijpharm.2006.04.023","volume":"319","author":"MS El-Samaligy","year":"2006","unstructured":"El-Samaligy MS, Afifi NA, Mahmoud EA. Evaluation of hybrid liposomes-encapsulated silymarin regarding physical stability and in vivo performance. Int J Pharm. 2006;319:121\u20139.","journal-title":"Int J Pharm"},{"issue":"1","key":"799_CR21","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0378-5173(02)00076-5","volume":"239","author":"P Ahlin","year":"2002","unstructured":"Ahlin P, Kristl J, Kristl A, Vre\u010der F. Investigation of polymeric nanoparticles as carriers of enalaprilat for oral administration. Int J Pharm. 2002;239(1):113\u201320.","journal-title":"Int J Pharm"},{"key":"799_CR22","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ijpharm.2005.11.006","volume":"308","author":"MS El-Samaligy","year":"2006","unstructured":"El-Samaligy MS, Afifi NN, Mahmoud EA. Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. Int J Pharm. 2006;308:140\u20138.","journal-title":"Int J Pharm"},{"issue":"6","key":"799_CR23","first-page":"1","volume":"9","author":"H Gao","year":"2012","unstructured":"Gao H, Li G, Lou M, Li X, Wei X, Wang J. Hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride-induced hepatic fibrosis. J Inflam. 2012;9(6):1\u20139.","journal-title":"J Inflam"},{"key":"799_CR24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.ijpharm.2011.04.041","volume":"413","author":"R Parveen","year":"2011","unstructured":"Parveen R, Baboota S, Ali J, Ahuja A, Vasudev S, Ahmad S. Oil based nanocarrier for improved oral delivery of silymarin: in vitro and in vivo studies. Int J Pharm. 2011;413:245\u201353.","journal-title":"Int J Pharm"},{"issue":"13","key":"799_CR25","first-page":"3031","volume":"8","author":"AC Egbuonu","year":"2009","unstructured":"Egbuonu AC, Obidoa O, Ezeokonkwo CA, Ezeanyika LU, Ejikeme PM. Hepatotoxic effects of low dose oral administration of monosodium glutamate in male albino rats. African J Biotech. 2009;8(13):3031\u20135.","journal-title":"African J Biotech"},{"issue":"3","key":"799_CR26","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1007\/s00580-012-1675-3","volume":"23","author":"OM Abdel-Salam","year":"2014","unstructured":"Abdel-Salam OM, Sleem AA, Shafee N. Hepatoprotective effects of Cynara extract and silymarin on carbon tetrachloride-induced hepatic damage in rats. Comp Clinl Path. 2014;23(3):709\u201316.","journal-title":"Comp Clinl Path"},{"key":"799_CR27","first-page":"1","volume":"38","author":"SK Mohan","year":"2009","unstructured":"Mohan SK, Priya V. Changes in lipid peroxidation, glutathione, ascorbic acid, vitamin E and antioxidant enzymes in patients with ovarian cancer. Acta Medica Academica. 2009;38:1\u20135.","journal-title":"Acta Medica Academica"},{"issue":"2","key":"799_CR28","doi-asserted-by":"crossref","first-page":"118","DOI":"10.31254\/phyto.2014.3207","volume":"3","author":"OB Adewale","year":"2014","unstructured":"Adewale OB, Adekeye AO, Akintayo CO, Onikanni A, Sabiu S. Carbon tetrachloride (CCl4) induced hepatic damage in experimental Sprague Dawley rats: antioxidant potential of Xylopia aethiopica. The Journal of Phytopharmacology. 2014;3(2):118\u201323.","journal-title":"The Journal of Phytopharmacology"},{"issue":"2","key":"799_CR29","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0378-4274(01)00456-8","volume":"126","author":"SE Gelperina","year":"2002","unstructured":"Gelperina SE, Khalansky AS, Skidan IN, Smirnova ZS, Bobruskin AI, Severin SE, et al. Toxicological studies of doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles in healthy rats and rats with intracranial glioblastoma. Toxicol Lett. 2002;126(2):131\u201341.","journal-title":"Toxicol Lett"},{"key":"799_CR30","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1111\/j.1440-1681.2007.04560.x","volume":"34","author":"MM Sayed-Ahmed","year":"2007","unstructured":"Sayed-Ahmed MM, Nagi MN. Thymoquinone supplementation prevents the development of gentamicin-induced acute renal toxicity in rats. Clin Exp Pharmacol Physiol. 2007;34:399\u2013405.","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"4","key":"799_CR31","first-page":"173","volume":"27","author":"M Peake","year":"2006","unstructured":"Peake M, Whiting M. Measurement of serum creatinine--current status and future goals. Clin Biochem Rev. 2006;27(4):173\u201384.","journal-title":"Clin Biochem Rev"},{"issue":"2","key":"799_CR32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","volume":"13","author":"P Costa","year":"2001","unstructured":"Costa P, Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123\u201333.","journal-title":"Eur J Pharm Sci"},{"issue":"1","key":"799_CR33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3329\/dujps.v8i1.5328","volume":"8","author":"AS Apu","year":"2009","unstructured":"Apu AS, Pathan AH, Kibria G, Jalil R. In vitro release kinetic study of theophylline from eudragit RS PO and eudragit RL PO matrix tablets. Dhaka Univ J Pharm Sci. 2009;8(1):1\u20136.","journal-title":"Dhaka Univ J Pharm Sci"},{"issue":"2","key":"799_CR34","doi-asserted-by":"crossref","first-page":"75","DOI":"10.3329\/dujps.v9i2.7883","volume":"9","author":"S Sadat","year":"2010","unstructured":"Sadat S, Islam M, Jahan S, Chowdhury J, Jalil R. Effect of cellulosic and Polymethacrylic polymers on drug content, particle morphology, and carbamazepine release profiles from sustained release ethyl cellulose microspheres. Dhaka J Pharm Sci. 2010;9(2):75\u201382.","journal-title":"Dhaka J Pharm Sci"},{"key":"799_CR35","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ijpharm.2015.04.067","volume":"489","author":"AN Allam","year":"2015","unstructured":"Allam AN, Komeil IA, Fouda MA, Abdallah OY. Preparation, characterization and in vivo evaluation of curcumin self-nano phospholipid dispersion as an approach to enhance oral bioavailability. Int J Pharm. 2015;489:117\u201323.","journal-title":"Int J Pharm"},{"issue":"2","key":"799_CR36","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.ijpharm.2006.11.061","volume":"336","author":"A Budhian","year":"2007","unstructured":"Budhian A, Siegel SJ, Winey KI. Haloperidol-loaded PLGA nanoparticles: systematic study of particle size and drug content. Int J Pharm. 2007;336(2):367\u201375.","journal-title":"Int J Pharm"},{"key":"799_CR37","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.ijpharm.2007.08.034","volume":"350","author":"X Song","year":"2008","unstructured":"Song X, Zhao Y, Wu W, Bi Y, Cai Z, Chen Q, et al. PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: systematic study of particle size and drug entrapment efficiency. Int J Pharm. 2008;350:320\u20139.","journal-title":"Int J Pharm"},{"issue":"12","key":"799_CR38","volume":"9","author":"DL Cooper","year":"2014","unstructured":"Cooper DL, Harirforoosh S. Effect of formulation variables on preparation of celecoxib loaded polylactide-co-glycolide nanoparticles. PLoS One. 2014;9(12):e113558.","journal-title":"PLoS One"},{"issue":"1","key":"799_CR39","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ijpharm.2006.01.041","volume":"314","author":"K Dillen","year":"2006","unstructured":"Dillen K, Vandervoort J, Van den Mooter G, Ludwig A. Evaluation of ciprofloxacin-loaded Eudragit\u00ae RS100 or RL100\/PLGA nanoparticles. Int J Pharm. 2006;314(1):72\u201382.","journal-title":"Int J Pharm"},{"key":"799_CR40","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.2217\/nnm.11.128","volume":"6","author":"S Das","year":"2011","unstructured":"Das S, Roy P, Auddy RG, Mukherjee A. Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity. Int J Nanomedicine. 2011;6:1291\u2013301.","journal-title":"Int J Nanomedicine"},{"issue":"4","key":"799_CR41","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1208\/s12249-011-9666-2","volume":"12","author":"R Lian","year":"2011","unstructured":"Lian R, Lu Y, Qi J, Tan Y, Niu M. Silymarin Glyceryl Monooleate\/Poloxamer 407 liquid crystalline matrices: physical characterization and enhanced oral bioavailability. AAPS PharmSciTech. 2011;12(4):1234\u201340.","journal-title":"AAPS PharmSciTech"},{"key":"799_CR42","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2478\/v10007-010-0038-3","volume":"60","author":"D Sonali","year":"2010","unstructured":"Sonali D, Tejal S, Vaishali T, Tejal G. Silymarin-solid dispersions: characterization and influence of preparation methods on dissolution. Acta Pharma. 2010;60:427\u201343.","journal-title":"Acta Pharma"},{"issue":"20","key":"799_CR43","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1056\/NEJMc060733","volume":"354","author":"N Mumoli","year":"2006","unstructured":"Mumoli N, Cei M, Cosimi A. Drug-related hepatotoxicity. N Engl J Med. 2006;354(20):2191\u20133.","journal-title":"N Engl J Med"},{"issue":"2","key":"799_CR44","first-page":"124","volume":"4","author":"MN Qureshi","year":"2010","unstructured":"Qureshi MN, Kuchekar BS, Logade NA, Haleem MA. In-vitro antioxidant and in-vivo Hepatoprotective a ctivity ofLeucas ciliata leaves. Rec Nat Prod. 2010;4(2):124\u201330.","journal-title":"Rec Nat Prod"},{"key":"799_CR45","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/cmi.2011.47","volume":"9","author":"E Zhao","year":"2012","unstructured":"Zhao E, Xu H, Wang L, Kryczek I, Wu K, Hu Y. Bone marrow and the control of immunity. Cell Mol Immunol. 2012;9:11\u20139.","journal-title":"Cell Mol Immunol"}],"container-title":["AAPS PharmSciTech"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/article\/10.1208\/s12249-017-0799-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-017-0799-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1208\/s12249-017-0799-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T17:32:51Z","timestamp":1659029571000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1208\/s12249-017-0799-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,17]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["799"],"URL":"https:\/\/doi.org\/10.1208\/s12249-017-0799-9","relation":{},"ISSN":["1530-9932"],"issn-type":[{"value":"1530-9932","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,17]]}}}