{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:54:23Z","timestamp":1790888063345,"version":"4.1.0"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,17]],"date-time":"2018-07-17T00:00:00Z","timestamp":1531785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673615 and 81503346"],"award-info":[{"award-number":["81673615 and 81503346"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The dry root of Scutellaria baicalensis, has traditionally been applied in the treatment of cerebral ischemia in Chinese clinics. Baicalin (BA) is considered the key ingredient in it for the brain protection effects. The bioavailability of BA is very low because of its poor lipid and water solubility, which limits the therapeutic effects and clinical application. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) formulation to improve the drug lipophilicity and further to enhance the drug-concentration in the brain tissues. This study is also designed to investigate the pharmacokinetics of BA in the pathological conditions of stroke and evaluate the pharmacokinetic differences of BA caused by stroke after intravenous administration with BA and BA-LP. In this study, the novel BA-LP prepared in early stage were characterized by morphology, size, zeta potential, encapsulation rate and the in vitro release. The pharmacokinetics and biodistribution of BA and BA-LP were investigated by intravenous administration in rats with middle cerebral artery occlusion (MCAO) model and normal group respectively. BA-LP had a mean particle size of 160\u2013190 nm, zeta potential of \u22125.7 mV, and encapsulation efficiency of 42 \u00b1 1%. The BA-LP showed a sustained-release behavior, the in vitro drug-release kinetic model of BA-LP fit well with the biphasic dynamic model equation: Q = 1 \u2212 (60.12e0.56t \u2212 59.08e0.0014t). Pharmacokinetic behavior in MCAO rats is not consistent with that of normal rats. The middle cerebral artery occlusion rats got higher Cmax and AUC0\u2013t, which were about 1.5\u20132 times to normal rats both in BA and liposome groups. In addition, it got especially higher distribution in brain, while BA were not detected in brain tissues on normal rats. The Cmax and AUC0\u2013t values were significantly greater with liposome than BA on both normal and MCAO rats. The tissue distribution behavior was significantly altered in the case of liposome administrated in comparison with BA, which the concentrations in the heart, liver, spleen, lungs and brain were all increased after administrated liposome, but decreased in kidneys. The TI values showed that the target of liposome was improved especially to heart, spleen and brain, and the brain\u2019s target was higher in striatum and cerebellum. In conclusion, BA-LP might be a potential drug delivery system to improve the therapeutic efficacy of BA. In addition, these results also suggest that the pathological damages of ischemia-reperfusion have a significant impact on the pharmacokinetic traits of BA.<\/jats:p>","DOI":"10.3390\/molecules23071747","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T08:45:42Z","timestamp":1531903542000},"page":"1747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Preparation, Characterization, Pharmacokinetics and Biodistribution of Baicalin-Loaded Liposome on Cerebral Ischemia-Reperfusion after i.v. Administration in Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Nan","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingling","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, No. 1166, Liutai Avenue, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine, The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine, Key Laboratory of Systematic Research, Development and Utilization of Chinese Medicine Resources in Sichuan Province\u2014Key Laboratory Breeding Base of Co-founded by Sichuan Province and MOST, Chengdu 611137, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1016\/S0024-3205(02)01920-3","article-title":"Hwangryun-Hae-Dok-tang (Huanglian-Jie-Du-Tang) extract and its constituents reduce ischemia-reperfusion brain injury and neutrophil infiltration in rats","volume":"71","author":"Hwang","year":"2002","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/S0378-8741(00)00303-2","article-title":"Protective effect of Oren-gedoku-to (Huang-Lian-Jie-Du-Tang) against impairment of learning and memory induced by transient cerebral ischemia in mice","volume":"73","author":"Xu","year":"2000","journal-title":"J. Ethnopharmacol."},{"key":"ref_3","first-page":"83","article-title":"Pharmacology, pharmacokinetics and toxicology of Chinese traditional medicine for stroke therapy","volume":"2","author":"Xiao","year":"2005","journal-title":"Asian J. Drug Metab. Pharmacokinet."},{"key":"ref_4","first-page":"519","article-title":"Effect of baicalin and dexamethasone on cytokines in brain tissue of infectious brain edema","volume":"25","author":"Yu","year":"2000","journal-title":"Bull. Hum. Med. Univ."},{"key":"ref_5","first-page":"630","article-title":"The protective effects of baicalin on pertussis bacilli-induced brain edema in rats","volume":"78","author":"Yang","year":"1998","journal-title":"Natl. Med. J. China"},{"key":"ref_6","first-page":"15","article-title":"Protective effects of scutellarria baicalensis stem-leaf total flavonid on the growth of human cervical carcinoma cell in vitro","volume":"45","author":"Wang","year":"2005","journal-title":"Shandong Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejphar.2007.03.037","article-title":"Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes","volume":"566","author":"Chang","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"ref_8","first-page":"743","article-title":"Protective effect of Baicalin on focal cerebral ischemia-reperfusion injury in rats","volume":"42","author":"Liu","year":"2007","journal-title":"Chin. Pharm. J."},{"key":"ref_9","first-page":"344","article-title":"Effects of Baicalin and gardenoside on oxygen-glucose deprivation and reperfusion injury in neurocytes","volume":"39","author":"Li","year":"2004","journal-title":"Chin. Pharm. J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.neuint.2008.09.004","article-title":"The flavonoid baicalin counteracts ischemic and oxidative insults to retinal cell and lipid peroxidation to brain membranes","volume":"53","author":"Jung","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.brainres.2006.09.063","article-title":"A comparative study on the individual and combined effects of baicalin and jasminoidin on focal cerebral ischemia-reperfusion injury","volume":"1123","author":"Zhang","year":"2006","journal-title":"Brain Res."},{"key":"ref_12","first-page":"374","article-title":"Pharmacokinetics of baicalin-phospholipid complex in rat plasma and brain tissues after intranasal and intravenous administration","volume":"66","author":"Li","year":"2011","journal-title":"Pharmazie"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1002\/jps.22573","article-title":"Evaluation of pharmacokinetic, biodistribution, pharmacodynamic, and toxicity profile of free juglone and its sterically stabilized liposomes","volume":"100","author":"Aithal","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jsps.2017.04.019","article-title":"Pharmacokinetics of a liposomal formulation of doxorubicin in rats","volume":"25","author":"Liu","year":"2017","journal-title":"Saudi Pharm. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.fitote.2010.01.004","article-title":"Comparative pharmacokinetics of baicalin in plasma after oral administration of Huang-Lian-Jie-Du-Tang or pure baicalin in MCAO and sham-operated rats","volume":"81","author":"Zeng","year":"2010","journal-title":"Fitoterapia"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.neuron.2014.03.003","article-title":"Stepwise recruitment of transcellular and paracellular pathways underlies blood-brain barrier break down in stroke","volume":"82","author":"Knowland","year":"2014","journal-title":"Neuron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.nbd.2008.08.005","article-title":"Blood-brain barrier tight junction permeability and ischemic stroke","volume":"32","author":"Sandoval","year":"2008","journal-title":"Neurobiol. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1002\/ptr.2062","article-title":"Antitumor activity of chloroform fraction of Scutellaria barbata and its active constituents","volume":"21","author":"Yu","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_19","first-page":"1805","article-title":"Novel nanoliposomal delivery system for polydatin: Preparation, characterization, and in vivo evaluation","volume":"9","author":"Wang","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3357","DOI":"10.1002\/jps.22534","article-title":"Preparation, Characterization, Pharmacokinetics, and Bioactivity of Honokiol-in-Hydroxypropyl-\u03b2-Cyclodextrin-in-Liposome","volume":"100","author":"Wang","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5889","DOI":"10.3390\/molecules20045889","article-title":"Formulations, Hemolytic and Pharmacokinetic Studies on Saikosaponin A and Saikosaponin D Compound Liposomes","volume":"20","author":"Zhang","year":"2015","journal-title":"Molecules"},{"key":"ref_22","first-page":"313","article-title":"Improved oral bioavailability of total flavonoids of Dracocephalum moldavica via composite phospholipid liposomes: Preparation, in-vitro drug release and pharmacokinetics in rats","volume":"12","author":"Zeng","year":"2016","journal-title":"Pharmacogn. Mag."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10847-011-0048-x","article-title":"Preparation and characterization of the inclusion complex of baicalein with \u03b3-cyclodextrin: An antioxidant ability study","volume":"73","author":"Li","year":"2012","journal-title":"J. Incl. Phenom. Macrocycl. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ijpharm.2011.01.055","article-title":"Preparation and characterization of baicalin-poly-vinylpyrrolidone coprecipitate","volume":"408","author":"Li","year":"2011","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ejps.2012.07.006","article-title":"Development and optimization of baicalin-loaded solid lipid nanoparticles prepared by coacervation method using central composite design","volume":"47","author":"Hao","year":"2012","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_26","first-page":"3623","article-title":"Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes","volume":"9","author":"Wei","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.2147\/IJN.S51578","article-title":"Nanoemulsion improves the oral bioavailability of baicalin in rats: In vitro and in vivo evaluation","volume":"8","author":"Zhao","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.jep.2004.06.009","article-title":"Effects of cerebral ischemia-reperfusion on pharmacokinetic fate of paeoniflorin after intravenous administration of Paeoniae Radix extract in rats","volume":"94","author":"He","year":"2004","journal-title":"J. Ethnopharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, Y.-T., Lu, Y., Hu, J.-C., Gong, Z.-P., Yang, W., Wang, A.-M., Zheng, J., Liu, T., Chen, T.-T., and Hu, J. (2016). Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula. Molecules, 21.","DOI":"10.3390\/molecules21091191"},{"key":"ref_30","first-page":"53","article-title":"Pharmacokinetic Effects of Baicalin on Cerebral Ischemiareperfusion after i.v. Administration in Rats","volume":"4","author":"Ma","year":"2012","journal-title":"Chin. Herb. Med."},{"key":"ref_31","first-page":"1824","article-title":"In-vivo studies on the pharmacokinetics of berberine on middle cerebral artery occlusion rat and sham-operated rat","volume":"5","author":"Pan","year":"2011","journal-title":"Afr. J. Pharm. Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/7\/1747\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:12:34Z","timestamp":1760195554000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/7\/1747"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,17]]},"references-count":31,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["molecules23071747"],"URL":"https:\/\/doi.org\/10.3390\/molecules23071747","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,17]]}}}