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A new cocrystal of isoniazid-quercetin with hepatoprotective effect: The design, structure, and in vitro/in vivo performance evaluation.
Eur J Pharm Sci 2020; 144:105216EJ

Abstract

With the purpose of overcoming the serious hepatotoxicity of antituberculosis drug isoniazid (INH), a cocrystallization strategy based on complementary advantages was implemented by choosing the hepatoprotective nutraceutical quercetin (QCT) as the cocrystal former. The strategy plays the solubility advantage of INH to improve the bioavailability of the insoluble QCT, thereby significantly enhancing the QCT's hepatoprotective effects. The optimized protective effects of QCT, in turn, feed back to INH to reduce its hepatotoxicity. Along this line, a novel INH-QCT cocrystal was successfully prepared and structurally characterized. The systematic evaluation results of the in vitro/in vivo revealed that, due to the advantage of INH's solubility, the dissolution efficiency of QCT from the cocrystal was increased 51.67-fold compared with that of coarse quercetin, and the oral bioavailability of the cocrystal in rats was enhanced by 28.91 times. As a result, the INH-QCT cocrystal almost removed INH induced serious hepatotoxicity, which has been demonstrated by the hepatotoxicity studies in rats. These findings present new opportunities for the advantageous solid forms of low-toxic antituberculosis drugs, and open new avenues against toxic side effects of drugs through the cocrystallization mean.

Authors+Show Affiliations

School of Medicine and Pharmacy and College of Marine Life Science, Ocean University of China, Qingdao, Shandong 266003, PR China; School of Pharmacy, Liaocheng University, Liaocheng, Shandong 252000, PR China.School of Medicine and Pharmacy and College of Marine Life Science, Ocean University of China, Qingdao, Shandong 266003, PR China.School of Medicine and Pharmacy and College of Marine Life Science, Ocean University of China, Qingdao, Shandong 266003, PR China.School of Medicine and Pharmacy and College of Marine Life Science, Ocean University of China, Qingdao, Shandong 266003, PR China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, 266003, PR China. Electronic address: yantuanli@ouc.edu.cn.School of Medicine and Pharmacy and College of Marine Life Science, Ocean University of China, Qingdao, Shandong 266003, PR China.School of Medicine and Pharmacy and College of Marine Life Science, Ocean University of China, Qingdao, Shandong 266003, PR China. Electronic address: cuiweiyan@ouc.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31945451

Citation

Liu, Fang, et al. "A New Cocrystal of Isoniazid-quercetin With Hepatoprotective Effect: the Design, Structure, and in Vitro/in Vivo Performance Evaluation." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 144, 2020, p. 105216.
Liu F, Wang LY, Yu MC, et al. A new cocrystal of isoniazid-quercetin with hepatoprotective effect: The design, structure, and in vitro/in vivo performance evaluation. Eur J Pharm Sci. 2020;144:105216.
Liu, F., Wang, L. Y., Yu, M. C., Li, Y. T., Wu, Z. Y., & Yan, C. W. (2020). A new cocrystal of isoniazid-quercetin with hepatoprotective effect: The design, structure, and in vitro/in vivo performance evaluation. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 144, p. 105216. doi:10.1016/j.ejps.2020.105216.
Liu F, et al. A New Cocrystal of Isoniazid-quercetin With Hepatoprotective Effect: the Design, Structure, and in Vitro/in Vivo Performance Evaluation. Eur J Pharm Sci. 2020 Jan 13;144:105216. PubMed PMID: 31945451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A new cocrystal of isoniazid-quercetin with hepatoprotective effect: The design, structure, and in vitro/in vivo performance evaluation. AU - Liu,Fang, AU - Wang,Ling-Yang, AU - Yu,Ming-Chao, AU - Li,Yan-Tuan, AU - Wu,Zhi-Yong, AU - Yan,Cui-Wei, Y1 - 2020/01/13/ PY - 2019/05/31/received PY - 2019/12/02/revised PY - 2020/01/12/accepted PY - 2020/1/17/pubmed PY - 2020/1/17/medline PY - 2020/1/17/entrez KW - Cocrystal KW - Hepatoprotective effect KW - In vitro/in vivo performance KW - Isoniazid KW - Quercetin SP - 105216 EP - 105216 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 144 N2 - With the purpose of overcoming the serious hepatotoxicity of antituberculosis drug isoniazid (INH), a cocrystallization strategy based on complementary advantages was implemented by choosing the hepatoprotective nutraceutical quercetin (QCT) as the cocrystal former. The strategy plays the solubility advantage of INH to improve the bioavailability of the insoluble QCT, thereby significantly enhancing the QCT's hepatoprotective effects. The optimized protective effects of QCT, in turn, feed back to INH to reduce its hepatotoxicity. Along this line, a novel INH-QCT cocrystal was successfully prepared and structurally characterized. The systematic evaluation results of the in vitro/in vivo revealed that, due to the advantage of INH's solubility, the dissolution efficiency of QCT from the cocrystal was increased 51.67-fold compared with that of coarse quercetin, and the oral bioavailability of the cocrystal in rats was enhanced by 28.91 times. As a result, the INH-QCT cocrystal almost removed INH induced serious hepatotoxicity, which has been demonstrated by the hepatotoxicity studies in rats. These findings present new opportunities for the advantageous solid forms of low-toxic antituberculosis drugs, and open new avenues against toxic side effects of drugs through the cocrystallization mean. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/31945451/A_new_cocrystal_of_isoniazid-quercetin_with_hepatoprotective_effect:_The_design,_structure,_and_in_vitro/in_vivo_performance_evaluation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(20)30005-1 DB - PRIME DP - Unbound Medicine ER -