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Current Drug Delivery

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ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

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Research Article

Formulation, Preparation, and Evaluation of Bifunctional Micelle with Glycyrrhizic Acid Containing Emodin for Toxicity Attenuation Application

Author(s): Qixiao Wang, Chenlu Gu, Michael Adu-Frimpong, Qiumin Xu, Hao Chi, Xiu Li, Clayton Takura Chingozho, Deerdi Meng, Haizhen Fu, Shanshan Tong* and Ximing Xu

Volume 21, Issue 4, 2024

Published on: 12 May, 2023

Page: [571 - 581] Pages: 11

DOI: 10.2174/1567201820666230502161936

Price: $65

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Abstract

Objective: To prepare GA-Emo micelles and investigate the feasibility of using GA as both a bifunctional drug and carrier.

Methods: The preparation of GA-Emo micelles was accomplished via the thin-film dispersion method with GA as the carrier. Size distribution, entrapment efficiency, and drug loading were used to evaluate the characteristics of micelles. The absorption and transport properties of the micelles in Caco-2 cells were investigated, while their pharmacodynamics in mice were preliminarily studied.

Results: The optimal formulation featured a GA/Emo in weight ratio of 2:1 and an encapsulation efficiency of 23.68%. The optimized GA/Emo was characterized as small uniform spheres with an average micellar size of 168.64 ± 5.69 nm, a polydispersity index of 0.17 ± 0.01, and an electrically negative surface (−35.33 ± 0.94 mV). Absorption and transport experiments with Caco-2 cells showed that the absorption of GA-Emo micelles in small intestines was mainly passive transport, amid their transport volume being significantly higher than that of Emo monomer. The intestinal wall thickness of the GAEmo micelles group was significantly lower than that of the Emo group, which meant that the colonic toxicity of the micelles was lower than unincorporated Emo.

Conclusion: The advantages of GA as a bifunctional micelle carrier in formulation characters, drug release, and toxicity attenuation provide a new idea for the application of the GA of natural medicine in drug delivery for toxicity reduction.

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[1]
Brough, C.; Williams, R.O., III Amorphous solid dispersions and nano-crystal technologies for poorly water-soluble drug delivery. Int. J. Pharm., 2013, 453(1), 157-166.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.061] [PMID: 23751341]
[2]
Göke, K.; Lorenz, T.; Repanas, A.; Schneider, F.; Steiner, D.; Baumann, K.; Bunjes, H.; Dietzel, A.; Finke, J.H.; Glasmacher, B.; Kwade, A. Novel strategies for the formulation and processing of poorly water-soluble drugs. Eur. J. Pharm. Biopharm., 2018, 126, 40-56.
[http://dx.doi.org/10.1016/j.ejpb.2017.05.008] [PMID: 28532676]
[3]
Hou, J.; Sun, E.; Zhang, Z.H.; Wang, J.; Yang, L.; Cui, L.; Ke, Z.C.; Tan, X.B.; Jia, X.B.; Lv, H. Improved oral absorption and anti-lung can-cer activity of paclitaxel-loaded mixed micelles. Drug Deliv., 2017, 24(1), 261-269.
[http://dx.doi.org/10.1080/10717544.2016.1245370] [PMID: 28165804]
[4]
Fahr, A.; Liu, X. Drug delivery strategies for poorly water-soluble drugs. Expert Opin. Drug Deliv., 2007, 4(4), 403-416.
[http://dx.doi.org/10.1517/17425247.4.4.403] [PMID: 17683253]
[5]
Jung, H.J.; Ahn, H.I.; Park, J.Y.; Ho, M.J.; Lee, D.R.; Cho, H.R.; Park, J.S.; Choi, Y.S.; Kang, M.J. Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate. Int. J. Biol. Macromol., 2016, 83, 282-287.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.11.063] [PMID: 26642839]
[6]
Joshi, H.N.; Tejwani, R.W.; Davidovich, M.; Sahasrabudhe, V.P.; Jemal, M.; Bathala, M.S.; Varia, S.A.; Serajuddin, A.T.M. Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in polyethylene glycol–polysorbate 80 mixture. Int. J. Pharm., 2004, 269(1), 251-258.
[http://dx.doi.org/10.1016/j.ijpharm.2003.09.002] [PMID: 14698596]
[7]
Wang, L.; Peng, M.; Zhu, Y.; Tong, S.S.; Cao, X.; Xu, X.M.; Yu, J.N. Preparation of pluronic/bile salt/phospholipid mixed micelles as drug solubility enhancer and study the effect of the PPO block size on the solubility of pyrene. Iran. J. Pharm. Res., 2014, 13(4), 1157-1163.
[PMID: 25587303]
[8]
Zhu, Y.; Yu, J.; Tong, S.; Wang, L.; Peng, M.; Cao, X.; Xu, X. Preparation and in vitro evaluation of povidone-sodium cholate-phospholipid mixed micelles for the solubilization of poorly soluble drugs. Arch. Pharm. Res., 2010, 33(6), 911-917.
[http://dx.doi.org/10.1007/s12272-010-0614-6] [PMID: 20607496]
[9]
Wang, G.; Wang, J.J.; Chen, X.L.; Du, L.; Li, F. Quercetin-loaded freeze-dried nanomicelles: Improving absorption and anti-glioma efficiency in vitro and in vivo. J. Control. Release, 2016, 235, 276-290.
[http://dx.doi.org/10.1016/j.jconrel.2016.05.045] [PMID: 27242199]
[10]
Shibata, S. A drug over the millennia: Pharmacognosy, chemistry, and pharmacology of licorice. Yakugaku Zasshi, 2000, 120(10), 849-862.
[http://dx.doi.org/10.1248/yakushi1947.120.10_849] [PMID: 11082698]
[11]
You, G.; Feng, T.; Zhang, G.; Chen, M.; Liu, F.; Sun, L.; Wang, M.; Ren, X. Preparation, optimization, characterization and in vitro release of baicalein-solubilizing glycyrrhizic acid nano-micelles. Int. J. Pharm., 2021, 601120546
[http://dx.doi.org/10.1016/j.ijpharm.2021.120546] [PMID: 33794322]
[12]
Wang, Y.; Zhao, B.; Wang, S.; Liang, Q.; Cai, Y.; Yang, F.; Li, G. Formulation and evaluation of novel glycyrrhizic acid micelles for trans-dermal delivery of podophyllotoxin. Drug Deliv., 2016, 23(5), 1623-1635.
[http://dx.doi.org/10.3109/10717544.2015.1135489] [PMID: 26786787]
[13]
Zhao, X.; Wu, Y.; Wang, D. Effects of glycyrrhizic acid on the pharmacokinetics of pristimerin in rats and its potential mechanism. Eur. J. Drug Metab. Pharmacokinet., 2018, 43(1), 63-68.
[http://dx.doi.org/10.1007/s13318-017-0423-0] [PMID: 28631076]
[14]
Hou, Y.C.; Lin, S.P.; Chao, P.D.L. Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A. Food Chem., 2012, 135(4), 2307-2312.
[http://dx.doi.org/10.1016/j.foodchem.2012.07.061] [PMID: 22980806]
[15]
Zhang, F.; Chen, H.; Lan, J.; Song, K.; Wu, X. Preparation and in vitro/in vivo evaluations of novel ocular micelle formulations of hesperetin with glycyrrhizin as a nanocarrier. Exp. Eye Res., 2021, 202108313
[http://dx.doi.org/10.1016/j.exer.2020.108313] [PMID: 33080302]
[16]
Chen, Y.; Xu, Y.; Zhang, H.; Yin, J.; Fan, X.; Liu, D.; Fu, H.; Wan, B. Emodin alleviates jejunum injury in rats with sepsis by inhibiting in-flammation response. Biomed. Pharmacother., 2016, 84, 1001-1007.
[http://dx.doi.org/10.1016/j.biopha.2016.10.031] [PMID: 27768925]
[17]
Dong, X.; Fu, J.; Yin, X.; Cao, S.; Li, X.; Lin, L.; Ni, J. Emodin: A review of its pharmacology, toxicity and pharmacokinetics. Phytother. Res., 2016, 30(8), 1207-1218.
[http://dx.doi.org/10.1002/ptr.5631] [PMID: 27188216]
[18]
Cheng, P.; Lan, W.; Yan-Hong, W.; Yun-Xia, L.; Yuan, P.; Yuan, P. The toxicity of aconitine, emodin on ICC cell and the anagonist effect of the compatibility. Eur. J. Drug Metab. Pharmacokinet., 2009, 34(3-4), 213-220.
[http://dx.doi.org/10.1007/BF03191176] [PMID: 20166441]
[19]
Li, Q.; Gao, J.; Pang, X.; Chen, A.; Wang, Y. Molecular mechanisms of action of emodin: As an anti-cardiovascular disease drug. Front. Pharmacol., 2020, 11559607
[http://dx.doi.org/10.3389/fphar.2020.559607] [PMID: 32973538]
[20]
Huang, W.; Chen, S.; Sun, L.; Wwang, H.; Qiao, H. Study on the intestinal permeability of lamivudine using Caco-2 cells monolayer and sin-gle-pass intestinal perfusion. Saudi J. Biol. Sci., 2022, 29(4), 2247-2252.
[http://dx.doi.org/10.1016/j.sjbs.2021.11.052] [PMID: 35531213]
[21]
Chen, C.; Li, T.; Chen, Z.; Wang, L.; Luo, X. Absorption rates and mechanisms of avenanthramides in a Caco-2 cell model and their antioxi-dant activity during absorption. J. Agric. Food Chem., 2020, 68(8), 2347-2356.
[http://dx.doi.org/10.1021/acs.jafc.9b06576] [PMID: 32026690]
[22]
Hubatsch, I.; Ragnarsson, E.G.E.; Artursson, P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nat. Protoc., 2007, 2(9), 2111-2119.
[http://dx.doi.org/10.1038/nprot.2007.303] [PMID: 17853866]
[23]
Li, J.; Tang, W.; Yang, Y.; Shen, Q.; Yu, Y.; Wang, X.; Fu, Y.; Li, C. A programmed cell‐mimicking nanoparticle driven by potato alkaloid for targeted cancer chemoimmunotherapy. Adv. Healthc. Mater., 2021, 10(13)2100311
[http://dx.doi.org/10.1002/adhm.202100311] [PMID: 33963820]
[24]
Wang, H.; Zheng, Y.; Sun, Q.; Zhang, Z.; Zhao, M.; Peng, C.; Shi, S. Ginsenosides emerging as both bifunctional drugs and nanocarriers for enhanced antitumor therapies. J. Nanobiotechnology, 2021, 19(1), 322.
[http://dx.doi.org/10.1186/s12951-021-01062-5] [PMID: 34654430]

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