{"data":{"id":"10.6084/m9.figshare.c.2130011.v1","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2130011.v1","prefix":"10.6084","suffix":"m9.figshare.c.2130011.v1","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Han, Xiaofeng","givenName":"Xiaofeng","familyName":"Han","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Zhe","givenName":"Zhe","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Manyuan","givenName":"Manyuan","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Li, Jing","givenName":"Jing","familyName":"Li","affiliation":[],"nameIdentifiers":[]},{"name":"Xu, Yongsong","givenName":"Yongsong","familyName":"Xu","affiliation":[],"nameIdentifiers":[]},{"name":"He, Rui","givenName":"Rui","familyName":"He","affiliation":[],"nameIdentifiers":[]},{"name":"Guan, Hongyu","givenName":"Hongyu","familyName":"Guan","affiliation":[],"nameIdentifiers":[]},{"name":"Yue, Zhujun","givenName":"Zhujun","familyName":"Yue","affiliation":[],"nameIdentifiers":[]},{"name":"Gong, Muxin","givenName":"Muxin","familyName":"Gong","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biochemistry"},{"subject":"Space Science"},{"subject":"Medicine"},{"subject":"Microbiology"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Pharmacology"},{"subject":"Chemical Sciences not elsewhere classified"},{"subject":"Sociology"},{"subject":"FOS: Sociology","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.c.2130011","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. \u003ci\u003eIn vitro\u003c/i\u003e release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and \u003ci\u003eC\u003c/i\u003e\u003csub\u003emax\u003c/sub\u003e level. Moreover, liver targeting drug delivery of micelles was confirmed by \u003ci\u003ein vivo\u003c/i\u003e imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl\u003csub\u003e4\u003c/sub\u003e, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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