| ORIGINAL ARTICLES |
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Optimized solubility and bioavailability of genistein based on cocrystal engineering |
| Zhipeng Wang1, Qi Li1, Qi An1, Lixiang Gong1, Shiying Yang1, Baoxi Zhang1, Bin Su3, Dezhi Yang1, Li Zhang1, Yang Lu1, Guanhua Du2 |
1. Beijing City Key Laboratory of Polymorphic Drugs, Center of Pharmaceutical Polymorphs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China;
2. Beijing City Key Laboratory of Drug Target and Screening Research, National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, People's Republic of China;
3. Shandong Soteria Pharmaceutical Co., Ltd., Laiwu, 271100, China |
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Abstract With various potential health-promoting bioactivities, genistein has great prospects in treatment of a series of complex diseases and metabolic syndromes such as cancer, diabetes, cardiovascular diseases, menopausal symptoms and so on. However, poor solubility and unsatisfactory bioavailability seriously limits its clinical application and market development. To optimize the solubility and bioavailability of genistein, the cocrystal of genistein and piperazine was prepared by grinding assisted with solvent based on the concept of cocrystal engineering. Using a series of analytical techniques including single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis, the cocrystal was characterized and confirmed. Then, structure analysis on the basis of theoretical calculation and a series of evaluation on the stability, dissolution and bioavailability were carried out. The results indicated that the cocrystal of genistein and piperazine improved the solubility and bioavailability of genistein. Compared with the previous studies on the cocrystal of genistein, this is a systematic and comprehensive investigation from the aspects of preparation, characterization, structural analysis, stability, solubility and bioavailability evaluation. As a simple, efficient and green approach, cocrystal engineering can pave a new path to optimize the pharmaceutical properties of natural products for successful drug formulation and delivery.
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| Keywords
Genistein
Piperazine
Cocrystal
Solubility
Bioavailability
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| Fund:This work was supported by the National Natural Science Foundation of China (Grant No. 22278443), CAMS Innovation Fund for Medical Sciences (Grant No. 2022-I2M-1-015), the Chinese Pharmacopoeia Commission Drug Standard Promoting Fund (Grant No. 2023Y11) for financial support. |
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Corresponding Authors:
Dezhi Yang,E-mail:ydz@imm.ac.cn;Li Zhang,E-mail:zhangl@imm.ac.cn;Yang Lu,E-mail:luy@imm.ac.cn
E-mail: zhangl@imm.ac.cn;luy@imm.ac.cn;ydz@imm.ac.cn;zhangl@imm.ac.cn;luy@imm.ac.cn
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Issue Date: 08 October 2023
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1. Rasheed S, Rehman K, Shahid M, et al. Therapeutic potentials of genistein: new insights and perspectives. J Food Biochem. 2022;46(9): e14228.
2. Rahman Mazumder MA, Hongsprabhas P. Genistein as antioxidant and antibrowning agents in in vivo and in vitro: a review. Biomed Pharmacother. 2016;82:379–92.
3. Neelakandan C, Chang T, Alexander T, et al. In Vitro evaluation of antioxidant and anti-inflammatory properties of genistein-modified hemodialysis membranes. Biomacromol. 2011;12(7):2447–55.
4. Spagnuolo C, Russo GL, Orhan IE, et al. Genistein and cancer: current status, challenges, and future directions. Adv Nutr. 2015;6(4):408–19.
5. Nazari-Khanamiri F, Ghasemnejad-Berenji M. Cellular and molecular mechanisms of genistein in prevention and treatment of diseases: an overview. J Food Biochem. 2021;45(11): e13972.
6. Jain R, Bolch C, Al-Nakkash L, et al. Systematic review of the impact of genistein on diabetes-related outcomes. Am J Physiol-Reg I. 2022;323(3):R279–88.
7. Kim EY, Hong KB, Suh HJ, et al. Protective effects of germinated and fermented soybean extract against tert-butyl hydroperoxide-induced hepatotoxicity in HepG2 cells and in rats. Food Funct. 2015;6(11):3512–21.
8. Thangavel P, Puga-Olguín A, Rodríguez-Landa JF, et al. Genistein as potential therapeutic candidate for menopausal symptoms and other related diseases. Molecules. 2019;24(21):3892–908.
9. Jafari S, Shoghi M, Khazdair MR, et al. Pharmacological effects of genistein on cardiovascular diseases. Evid-Based Compl Alt. 2023;2023:1–16.
10. Ko EA, Park WS, Son YK, et al. The effect of tyrosine kinase inhibitor genistein on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells. Vasc Pharmacol. 2009;50(1–2):51–6.
11. Kojima T, Uesugi T, Toda T, et al. Hypolipidemic action of the soybean isoflavones genistein and genistin in glomerulonephritic rats. Lipids. 2002;37(3):261–5.
12. Yu L, Rios E, Castro L, et al. Genistein: dual role in women’s health. Nutrients. 2021;13(9):3048–70.
13. Buddhiranon S, Kyu T. Solubilization of genistein in poly (oxyethylene) through eutectic crystal melting. J Phys Chem B. 2012;116(27):7795–802.
14. Polkowski K, Skierski JS, Mazurek AP. Anticancer activity of genistein-piperazine complex. In vitro study with HL-60 cells. Acta Pol Pharm. 2000;57(3):223–31.
15. Daruházi ÁE, Szente L, Balogh B, et al. Utility of cyclodextrins in the formulation of genistein. J Pharmaceut Biomed. 2008;48(3):636–40.
16. Stancanelli R, Mazzaglia A, Tommasini S, et al. The enhancement of isoflavones water solubility by complexation with modified cyclodextrins: a spectroscopic investigation with implications in the pharmaceutical analysis. J Pharmaceut Biomed. 2007;44(4):980–4.
17. Zhang W, Li X, Ye T, et al. Design, characterization, and in vitro cellular inhibition and uptake of optimized genistein-loaded NLC for the prevention of posterior capsular opacification using response surface methodology. Int J Pharmaceut. 2013;454(1):354–66.
18. Aditya NP, Shim M, Lee I, et al. Curcumin and genistein coloaded nanostructured lipid carriers: in vitro digestion and antiprostate cancer activity. J Agr Food Chem. 2013;61(8):1878–83.
19. Jaiswal N, Akhtar J, Singh SP, et al. An overview on genistein and its various formulations. Drug Res. 2018;69(06):305–13.
20. Wang Z, Xie Y, Yu M, et al. Recent advances on the biological study of pharmaceutical cocrystals. AAPS PharmSciTech. 2022;23(8):303.
21. Guo M, Sun X, Chen J, et al. Pharmaceutical cocrystals: a review of preparations, physicochemical properties and applications. Acta Pharm Sin B. 2021;11(8):2537–64.
22. Emami S, Siahi-Shadbad M, Adibkia K, et al. Recent advances in improving oral drug bioavailability by cocrystals. Bioimpacts. 2018;8(4):305–20.
23. Panzade PS, Shendarkar GR. Pharmaceutical cocrystal: a game changing approach for the administration of old drugs in new crystalline form. Drug Dev Ind Pharm. 2020;46(10):1559–68.
24. Dai XL, Yao J, Wu C, et al. Solubility and permeability improvement of allopurinol by cocrystallization. Cryst Growth Des. 2020;20(8):5160–8.
25. Wang JR, Wang X, Yang Y, et al. Solid-state characterization of 17β-estradiol co-crystals presenting improved dissolution and bioavailability. CrystEngComm. 2016;18(19):3498–505.
26. Chatziadi A, Skorepova E, Jirat J, et al. Characterization and insights into the formation of new multicomponent solid forms of sofosbuvir. Cryst Growth Des. 2022;22(5):3395–404.
27. Yan Y, Dai XL, Jia JL, et al. Crystal structures, stability, and solubility evaluation of two polymorphs of a 2:1 melatonin-piperazine cocrystal. Cryst Growth Des. 2019;20(2):1079–87.
28. He H, Huang Y, Zhang Q, et al. Zwitterionic cocrystals of flavonoids and proline: solid-state characterization, pharmaceutical properties, and pharmacokinetic performance. Cryst Growth Des. 2016;16(4):2348–56.
29. Sowa M, Ślepokura K, Matczak-Jon E. Cocrystals of fisetin, luteolin and genistein with pyridinecarboxamide coformers: crystal structures, analysis of intermolecular interactions, spectral and thermal characterization. CrystEngComm. 2013;15(38):7696–708.
30. Sowa M, Ślepokura K, Matczak-Jon E. A 1:2 cocrystal of genistein with isonicotinamide: crystal structure and Hirshfeld surface analysis. Acta Crystallogr C. 2013;69(11):1267–72.
31. Sowa M, Ślepokura K, Matczak-Jon E. Solid-state characterization and solubility of a genistein–caffeine cocrystal. J Mol Struct. 2014;1076:80–8.
32. Zhang Y, Zhu B, Ji WJ, et al. Insight into the formation of cocrystals of flavonoids and 4,4'-vinylenedipyridine: heteromolecular hydrogen bonds, molar ratio, and structural analysis. Cryst Growth Des. 2021;21(5):2720–33.
33. Zhang YN, Yin HM, Zhang Y, et al. Preparation of a 1:1 cocrystal of genistein with 4,4'-bipyridine. J Cryst Growth. 2017;458:103–9.
34. Li X, Liu X, Song J, et al. Drug–drug cocrystallization simultaneously improves pharmaceutical properties of genistein and ligustrazine. Cryst Growth Des. 2021;21(6):3461–8.
35. Wu B, Kulkarni K, Basu S, et al. First-pass metabolism via UDP-glucuronosyltransferase: a barrier to oral bioavailability of phenolics. J Pharm Sci. 2011;100(9):3655–81.
36. Tang L, Feng Q, Zhao J, et al. Involvement of UDP-glucuronosyltranferases and sulfotransferases in the liver and intestinal first-pass metabolism of seven flavones in C57 mice and humans in vitro. Food Chem Toxicol. 2012;50(5):1460–7.
37. McClain RM, Wolz E, Davidovich A, et al. Acute, subchronic and chronic safety studies with genistein in rats. Food Chem Toxicol. 2006;44(1):56–80.
38. Ullmann U, Metzner J, Frank T, et al. Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (BonisteinTM) in healthy volunteers. Adv Ther. 2005;22:65–78.
39. Frisch M, Trucks G, Schlegel H, et al. Gaussian 16. Wallingford: Gaussian. Inc.; 2016.
40. Yang D, Cao J, Heng T, et al. Theoretical calculation and structural analysis of the cocrystals of three flavonols with praziquantel. Cryst Growth Des. 2021;21(4):2292–300.
41. Nguyen ALP, Izgorodina EI. Behavior of counterpoise correction in many-body molecular clusters of organic compounds: Hartree-Fock interaction energy perspective. J Comput Chem. 2022;43(8):568–76.
42. Lu T, Chen Q. Independent gradient model based on Hirshfeld partition: a new method for visual study of interactions in chemical systems. J Comput Chem. 2022;43(8):539–55.
43. Spackman PR, Turner MJ, McKinnon JJ, et al. CrystalExplorer: a program for Hirshfeld surface analysis, visualization and quantitative analysis of molecular crystals. J Appl Crystallogr. 2021;54(3):1006–11. |
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