Enhancement of Oral Bioavailability and Anti-hyperuricemic Activity of Isoliquiritigenin via Self-Microemulsifying Drug Delivery System
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The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (− 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.
Key WordsIsoliquiritigenin ISL-SMEDDS bioavailability in vitro release anti-hyperuricemic
The authors thank the Jiangsu University Ethics Committee for their kind guidance in the animal experiments.
This work was supported by the National Natural Science Foundation of China (81503025, 81473172, and 81773695), China Postdoctoral Science Foundation (2017M621658 and 2017M621659), and Special Funds for 331 and 333 projects (BRA2013198).
Compliance with Ethical Standards
The protocol for the experiment was in compliance with Jiangsu University’s Ethics Committee and guidelines spelt out for animal study by National Institute for Care and Use of Laboratory Animals (UJS-IACUC-2019032202).
Conflict of Interest
The authors declare that they have no conflict of interest.
- 2.Yaling H, Chunchieh C, Chen PJ, Huang SE, Huang SC, Polin K. Shallot and licorice constituent isoliquiritigenin arrests cell cycle progression and induces apoptosis through the induction of ATM/p53 and initiation of the mitochondrial system in human cervical carcinoma HeLa cells. Mol Nutr Food Res. 2010;53:826–35.Google Scholar
- 8.Zhang, D. H.; Lan-Lan, Y. E.; Cheng, H.; Wei, Y. U.; Yang, J. Cytoprotective effect and its mechanisms of isoliquiritigenin on acetaminophen induced acute injury of hepatocytes. CJCPT. 2008;13:293-298.Google Scholar
- 14.Zhou, J. X.; Lin, W. U.; Wang, J. G. Technology preparation of isoliquiritigenin microcapsule and their release in vitro. Mod Food Sci Tech. 2010;10:1132-5.Google Scholar
- 16.Chen, C.; Cai, D.; Qin, P.; Chen, B.; Wang, Z.; Tan, T. Bio-plasticizer production by hybrid acetone-butanol-ethanol fermentation with full cell catalysis of Candida sp. 99–125. Bioresour Technol. 2018; 257:217-22.Google Scholar
- 17.Al BGE. SMEDDS: a novel approach for lipophilic drugs. Int J Pharm Sci. 2012;3:2441-2450.Google Scholar
- 19.W N, C. Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts. J Pharm Sci. 2000;89:967–978.Google Scholar
- 21.Mezghrani, O.; Ke, X.; Bourkaib, N.; Xu, B. H. Optimized self-microemulsifying drug delivery systems (SMEDDS) for enhanced oral bioavailability of astilbin. Pharmazie. 2011;66:754–60.Google Scholar
- 28.Xie, Y. J.; Wang, Q. L.; Adu-Frimpong, M., et al. Preparation and evaluation of isoliquiritigenin-loaded F127/P123 polymeric micelles. Drug Devel Ind Pharm. 2019;1:29.Google Scholar
- 31.Qureshi MJ, Mallikarjun C, Kian WG. Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: a study in diet induced hyperlipidemic rabbits. Asi J Pharm Sci. 2015;10:40–56.CrossRefGoogle Scholar
- 38.Balata, G. F.; Essa, E. A.; Shamardl, H. A.; Zaidan, S. H.; Abourehab, M. A. Therapy self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol. Drug Des Devel Ther. 2016; 10:117–28.Google Scholar
- 42.Qureshi, M. J.; Mallikarjun, C.; Kian, W. G. Enhancement of solubility and therapeutic potential of poorly soluble lovastatin by SMEDDS formulation adsorbed on directly compressed spray dried magnesium aluminometasilicate liquid loadable tablets: a study in diet induced hyperlipidemic rabbits. Asia J Pharm Sci. 2015;10:40–56.CrossRefGoogle Scholar
- 46.Parul, J.; Geeta, A.; Sasidharan Leelakumari, H.; Kashmir, S. Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan. Int J Pharm Investig. 2014;4:195–206.Google Scholar
- 48.Wang Y, Wang S, Firempong CK, et al. Enhanced solubility and bioavailability of naringenin via liposomal nanoformulation: preparation and in vitro and in vivo evaluations. AAPS PharmSciTech. 2016;18:1–9.Google Scholar
- 49.Kumar P, Das A, Savant SS, Mandal RK, Hassan S. Gout nodulosis: report of a rare case and brief review. Dermatol Online J. 2015;21:8.Google Scholar