{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:14:48Z","timestamp":1784304888898,"version":"3.55.0"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["81670456"],"award-info":[{"award-number":["81670456"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7162132"],"award-info":[{"award-number":["7162132"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Fund for Medical Sciences","award":["2017-I2M-1-011"],"award-info":[{"award-number":["2017-I2M-1-011"]}]},{"name":"the grant from the Key National Basic Research Program of China","award":["2018RC350008"],"award-info":[{"award-number":["2018RC350008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.<\/jats:p>","DOI":"10.3390\/pharmaceutics12100906","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T02:56:43Z","timestamp":1600916203000},"page":"906","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats"],"prefix":"10.3390","volume":"12","author":[{"given":"Shuyue","family":"Ren","sequence":"first","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Drug Targets Identification and Drug Screening, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingtai","family":"Jiao","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiying","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junke","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Drug Targets Identification and Drug Screening, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoying","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Drug Targets Identification and Drug Screening, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingrong","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Drug Targets Identification and Drug Screening, 1 Xian Nong Tan Street, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Lv","sequence":"additional","affiliation":[{"name":"Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China"},{"name":"Beijing Key Laboratory of Drug Targets Identification 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