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ISSN (Online): 2210-3163

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Mini-Review Article

A Review of Various Pharmacological Effects of Quercetin with its Barriers and Approaches for Solubility and Permeability Enhancement

Author(s): Rakesh Mishra * and Shweta Kulkarni

Volume 12, Issue 4, 2022

Published on: 14 January, 2022

Article ID: e151021197263 Pages: 13

DOI: 10.2174/2210315511666211015122340

Price: $65

Abstract

Background: Quercetin, one of the most beneficial flavonoids, has been included in the human diet due to its therapeutic effect on health. Recently, quercetin has been gaining scientific attraction for its multifarious activities, including anti-oxidant, anti-inflammatory, antiviral, anti-diabetic, anti-cancer, and anti-arthritic activities and its function in easing some cardiovascular diseases. However, these applications of quercetin in the pharmaceutical field are limited due to its poor aqueous solubility and poor permeability.

Objective: The present review summarizes various pharmacological activities of quercetin, analyzes the barriers like solubility and permeability, which restrict the therapeutic efficiency of quercetin, and also discusses novel approaches to enhance aqueous solubility and permeability of quercetin for its effective clinical use.

Methods: The current review information sources were peer-reviewed relevant scientific articles of recognized journals from scientific engines and databases (Scopus, Web of Science, PubMed, Science Direct, Google Scholar) using different keywords related to quercetin pharmacological effects, mechanism, solubility, permeability, absorption barriers, and formulation approaches.

Results: Various novel approaches, including solid dispersions, inclusion complex, pro-drugs, nanoemulsion, micelles, liposomes, SNEEDS, and microspheres, have been developed to overcome the solubility and permeability barriers for efficient quercetin delivery.

Conclusion: This review revealed that the multifaceted pharmacological activities of quercetin for the management of various diseases are enormously dependent on the development of novel and safe drug delivery systems of quercetin.

Keywords: Quercetin, flavonoids, pharmacological activities, novel approaches, aqueous solubility, permeability.

Graphical Abstract

[1]
D’Andrea, G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia, 2015, 106(106), 256-271.
[http://dx.doi.org/10.1016/j.fitote.2015.09.018] [PMID: 26393898]
[2]
Xiao, L.; Luo, G.; Tang, Y.; Yao, P. Quercetin and iron metabolism: What we know and what we need to know. Food Chem. Toxicol., 2018, 114, 190-203.
[http://dx.doi.org/10.1016/j.fct.2018.02.022] [PMID: 29432835]
[3]
Anand David, A.V.; Arulmoli, R.; Parasuraman, S. Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn. Rev., 2016, 10(20), 84-89.
[http://dx.doi.org/10.4103/0973-7847.194044] [PMID: 28082789]
[4]
Ohnishi, E.; Bannai, H. Quercetin potentiates TNF-induced antiviral activity. Antiviral Res., 1993, 22(4), 327-331.
[http://dx.doi.org/10.1016/0166-3542(93)90041-G] [PMID: 8279819]
[5]
Thapa, M.; Kim, Y.; Desper, J.; Chang, K.O.; Hua, D.H. Synthesis and antiviral activity of substituted quercetins. Bioorg. Med. Chem. Lett., 2012, 22(1), 353-356.
[http://dx.doi.org/10.1016/j.bmcl.2011.10.119] [PMID: 22115591]
[6]
Natarajan, V.; Krithica, N.; Madhan, B.; Sehgal, P.K. Formulation and evaluation of quercetin polycaprolactone microspheres for the treatment of rheumatoid arthritis. J. Pharm. Sci., 2011, 100(1), 195-205.
[http://dx.doi.org/10.1002/jps.22266] [PMID: 20607810]
[7]
Nabavi, S.F.; Russo, G.L.; Daglia, M.; Nabavi, S.M. Role of quercetin as an alternative for obesity treatment: You are what you eat! Food Chem., 2015, 179, 305-310.
[http://dx.doi.org/10.1016/j.foodchem.2015.02.006] [PMID: 25722169]
[8]
Mukhopadhyay, P.; Prajapati, A.K. Quercetin in anti-diabetic research and strategies for improved quercetin bioavailability using polymer-based carriers a review. RSC Adv., 2015, 5(118), 97547-97562.
[http://dx.doi.org/10.1039/C5RA18896B]
[9]
Li, Y.; Yao, J.; Han, C.; Yang, J.; Chaudhry, M.T.; Wang, S.; Liu, H.; Yin, Y. Quercetin, inflammation and immunity. Nutrients, 2016, 8(3), 167.
[http://dx.doi.org/10.3390/nu8030167] [PMID: 26999194]
[10]
Chen, S.; Jiang, H.; Wu, X.; Fang, J. Therapeutic effects of quercetin on inflammation, obesity, and type 2 diabetes. Mediators Inflamm., 2016, 2016, 9340637.
[11]
Patel, R.V.; Mistry, B.M.; Shinde, S.K.; Syed, R.; Singh, V.; Shin, H.S. Therapeutic potential of quercetin as a cardiovascular agent. Eur. J. Med. Chem., 2018, 155, 889-904.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.053] [PMID: 29966915]
[12]
Milanezi, F.G.; Meireles, L.M.; de Christo Scherer, M.M.; de Oliveira, J.P.; da Silva, A.R.; de Araujo, M.L.; Endringer, D.C.; Fronza, M.; Guimarães, M.C.C.; Scherer, R. Antioxidant, antimicrobial and cytotoxic activities of gold nanoparticles capped with quercetin. Saudi Pharm. J., 2019, 27(7), 968-974.
[http://dx.doi.org/10.1016/j.jsps.2019.07.005] [PMID: 31997903]
[13]
Li, G.; Shen, X.; Wei, Y.; Si, X.; Deng, X.; Wang, J. Quercetin reduces Streptococcus suis virulence by inhibiting suilysin activity and inflammation. Int. Immunopharmacol., 2019, 69, 71-78.
[http://dx.doi.org/10.1016/j.intimp.2019.01.017] [PMID: 30682719]
[14]
Zaplatic, E.; Bule, M.; Shah, S.Z.A.; Uddin, M.S.; Niaz, K.; Niaz, K. Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer’s disease. Life Sci., 2019, 224, 109-119.
[http://dx.doi.org/10.1016/j.lfs.2019.03.055] [PMID: 30914316]
[15]
Jafarinia, M.; Sadat Hosseini, M.; Kasiri, N.; Fazel, N.; Fathi, F.; Ganjalikhani Hakemi, M.; Eskandari, N. Quercetin with the potential effect on allergic diseases. Allergy Asthma Clin. Immunol., 2020, 16(1), 36.
[http://dx.doi.org/10.1186/s13223-020-00434-0] [PMID: 32467711]
[16]
Tang, S.M.; Deng, X.T.; Zhou, J.; Li, Q.P.; Ge, X.X.; Miao, L. Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. Biomed. Pharmacother., 2020, 121, 109604.
[http://dx.doi.org/10.1016/j.biopha.2019.109604] [PMID: 31733570]
[17]
Khursheed, R.; Singh, S.K.; Wadhwa, S.; Gulati, M.; Awasthi, A. Enhancing the potential preclinical and clinical benefits of quercetin through novel drug delivery systems. Drug Discov. Today, 2020, 25(1), 209-222.
[http://dx.doi.org/10.1016/j.drudis.2019.11.001] [PMID: 31707120]
[18]
Ulusoy, H.G.; Sanlier, N. A minireview of quercetin: From its metabolism to possible mechanisms of its biological activities. Crit. Rev. Food Sci. Nutr., 2020, 60(19), 3290-3303.
[http://dx.doi.org/10.1080/10408398.2019.1683810] [PMID: 31680558]
[19]
Wang, W.; Sun, C.; Mao, L.; Ma, P.; Liu, F.; Yang, J. The biological activities, chemical stability, metabolism and delivery systems of quercetin: A review. Trends Food Sci. Technol., 2016, 56, 21-38.
[http://dx.doi.org/10.1016/j.tifs.2016.07.004]
[20]
Gupta, A.; Birhman, K.; Raheja, I.; Sharma, S.K.; Kar, H.K. Quercetin: A wonder bioflavonoid with therapeutic potential in disease management. Asian Pac. J. Trop. Dis., 2016, 6(3), 248-252.
[http://dx.doi.org/10.1016/S2222-1808(15)61024-6]
[21]
Wang, Y.; Tao, B.; Wan, Y.; Sun, Y.; Wang, L.; Sun, J.; Li, C. Drug delivery based pharmacological enhancement and current insights of quercetin with therapeutic potential against oral diseases. Biomed. Pharmacother., 2020, 128, 110372.
[http://dx.doi.org/10.1016/j.biopha.2020.110372] [PMID: 32521458]
[22]
Yoon, J.S.; Chae, M.K.; Lee, S.Y.; Lee, E.J. Anti-inflammatory effect of quercetin in a whole orbital tissue culture of Graves’ orbitopathy. Br. J. Ophthalmol., 2012, 96(8), 1117-1121.
[http://dx.doi.org/10.1136/bjophthalmol-2012-301537] [PMID: 22661653]
[23]
Lesjak, M.; Beara, I.; Simin, N.; Pintać, D.; Majkić, T.; Bekvalac, K. Anti-oxidant and anti-inflammatory activities of quercetin and its derivatives. J. Funct. Foods, 2018, 40, 68-75.
[http://dx.doi.org/10.1016/j.jff.2017.10.047]
[24]
Fan, D.; Zhou, X.; Zhao, C.; Chen, H.; Zhao, Y.; Gong, X. Anti-inflammatory, antiviral and quantitative study of quercetin-3-O-β-D-glucuronide in Polygonum perfoliatum L. Fitoterapia, 2011, 82(6), 805-810.
[http://dx.doi.org/10.1016/j.fitote.2011.04.007] [PMID: 21570451]
[25]
Maalik, A.; Khan, F.A.; Mumtaz, A.; Mehmood, A.; Azhar, S.; Atif, M. Pharmacological applications of quercetin and its derivatives: A short review. Trop. J. Pharm. Res., 2014, 13(9), 1561-1566.
[http://dx.doi.org/10.4314/tjpr.v13i9.26]
[26]
Wu, W.; Li, R.; Li, X.; He, J.; Jiang, S.; Liu, S.; Yang, J. Quercetin as an antiviral agent inhibits Influenza A Virus (IAV) entry. Viruses, 2015, 8(1), 6.
[http://dx.doi.org/10.3390/v8010006] [PMID: 26712783]
[27]
Babacanoglu, C.; Yildirim, N.; Sadi, G.; Pektas, M.B.; Akar, F. Resveratrol prevents high-fructose corn syrup-induced vascular insulin resistance and dysfunction in rats. Food Chem. Toxicol., 2013, 60, 160-167.
[http://dx.doi.org/10.1016/j.fct.2013.07.026] [PMID: 23872130]
[28]
Shi, G.J.; Li, Y.; Cao, Q.H.; Wu, H.X.; Tang, X.Y.; Gao, X.H.; Yu, J.Q.; Chen, Z.; Yang, Y. In vitro and in vivo evidence that quercetin protects against diabetes and its complications: A systematic review of the literature. Biomed. Pharmacother., 2019, 109, 1085-1099.
[http://dx.doi.org/10.1016/j.biopha.2018.10.130] [PMID: 30551359]
[29]
Fu, J.; Huang, J.; Lin, M.; Xie, T.; You, T. Quercetin promotes diabetic wound healing via switching macrophages from M1 to M2 polarization. J. Surg. Res., 2020, 246, 213-223.
[http://dx.doi.org/10.1016/j.jss.2019.09.011] [PMID: 31606511]
[30]
Haleagrahara, N.; Miranda-Hernandez, S.; Alim, M.A.; Hayes, L.; Bird, G.; Ketheesan, N. Therapeutic effect of quercetin in collagen-induced arthritis. Biomed. Pharmacother., 2017, 90, 38-46.
[http://dx.doi.org/10.1016/j.biopha.2017.03.026] [PMID: 28342364]
[31]
Gokhale, J.P.; Mahajan, H.S.; Surana, S.J. Quercetin loaded nanoemulsion-based gel for rheumatoid arthritis: In vivo and in vitro studies. Biomed. Pharmacother., 2019, 112, 108622.
[http://dx.doi.org/10.1016/j.biopha.2019.108622] [PMID: 30797146]
[32]
Yuan, K.; Zhu, Q.; Lu, Q.; Jiang, H.; Zhu, M.; Li, X.; Huang, G.; Xu, A. Quercetin alleviates rheumatoid arthritis by inhibiting neutrophil inflammatory activities. J. Nutr. Biochem., 2020, 84, 108454.
[http://dx.doi.org/10.1016/j.jnutbio.2020.108454] [PMID: 32679549]
[33]
Volate, S.R.; Davenport, D.M.; Muga, S.J.; Wargovich, M.J. Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin). Carcinogenesis, 2005, 26(8), 1450-1456.
[http://dx.doi.org/10.1093/carcin/bgi089] [PMID: 15831530]
[34]
Murakami, A.; Ashida, H.; Terao, J. Multitargeted cancer prevention by quercetin. Cancer Lett., 2008, 269(2), 315-325.
[http://dx.doi.org/10.1016/j.canlet.2008.03.046] [PMID: 18467024]
[35]
Zheng, S.Y.; Li, Y.; Jiang, D.; Zhao, J.; Ge, J.F. Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549. Mol. Med. Rep., 2012, 5(3), 822-826.
[PMID: 22200874]
[36]
Kobori, M. Dietary Quercetin and other Polyphenols: Attenuation of Obesity.In: Polyphenols in Human Health and Disease Academic Press: USA, 2013, pp163-175.
[http://dx.doi.org/10.1016/B978-0-12-398456-2.00014-1]
[37]
Kim, C.S.; Kwon, Y.; Choe, S.Y.; Hong, S.M.; Yoo, H.; Goto, T.; Kawada, T.; Choi, H.S.; Joe, Y.; Chung, H.T.; Yu, R. Quercetin reduces obesity-induced hepatosteatosis by enhancing mitochondrial oxidative metabolism via heme oxygenase-1. Nutr. Metab. (Lond.), 2015, 12(1), 33.
[http://dx.doi.org/10.1186/s12986-015-0030-5] [PMID: 26445592]
[38]
Nettore, I.C.; Rocca, C.; Mancino, G.; Albano, L.; Amelio, D.; Grande, F.; Puoci, F.; Pasqua, T.; Desiderio, S.; Mazza, R.; Terracciano, D.; Colao, A.; Bèguinot, F.; Russo, G.L.; Dentice, M.; Macchia, P.E.; Sinicropi, M.S.; Angelone, T.; Ungaro, P. Quercetin and its derivative Q2 modulate chromatin dynamics in adipogenesis and Q2 prevents obesity and metabolic disorders in rats. J. Nutr. Biochem., 2019, 69, 151-162.
[http://dx.doi.org/10.1016/j.jnutbio.2019.03.019] [PMID: 31096072]
[39]
Larson, A.J.; Symons, J.D.; Jalili, T. Therapeutic potential of quercetin to decrease blood pressure: Review of efficacy and mechanisms. Adv. Nutr., 2012, 3(1), 39-46.
[http://dx.doi.org/10.3945/an.111.001271] [PMID: 22332099]
[40]
Duarte, J.; Pérez-Vizcaíno, F.; Zarzuelo, A.; Jiménez, J.; Tamargo, J. Vasodilator effects of quercetin in isolated rat vascular smooth muscle. Eur. J. Pharmacol., 1993, 239(1-3), 1-7.
[http://dx.doi.org/10.1016/0014-2999(93)90968-N] [PMID: 8223884]
[41]
Cohn, J.N. Role of the renin-angiotensin system in cardiovascular disease. Cardiovasc. Drugs Ther., 2010, 24(4), 341-344.
[http://dx.doi.org/10.1007/s10557-010-6230-3] [PMID: 20454841]
[42]
Häckl, L.P.N.; Cuttle, G.; Dovichi, S.S.; Lima-Landman, M.T.; Nicolau, M. Inhibition of angiotesin-converting enzyme by quercetin alters the vascular response to brandykinin and angiotensin I. Pharmacology, 2002, 65(4), 182-186.
[http://dx.doi.org/10.1159/000064341] [PMID: 12174832]
[43]
Bondonno, N.P.; Bondonno, C.P.; Hodgson, J.M.; Ward, N.C.; Croft, K.D. The efficacy of quercetin in cardiovascular health. Curr. Nutr. Rep., 2015, 4(4), 290-303.
[http://dx.doi.org/10.1007/s13668-015-0137-3]
[44]
Böhm, F.; Pernow, J. The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc. Res., 2007, 76(1), 8-18.
[http://dx.doi.org/10.1016/j.cardiores.2007.06.004] [PMID: 17617392]
[45]
Deng, Q.; Li, X.X.; Fang, Y.; Chen, X.; Xue, J. Therapeutic potential of quercetin as an antiatherosclerotic agent in atherosclerotic cardiovascular disease: A review. Evid.-Based Complement. Altern. Med., 2020, 2020, 5926381.
[46]
Pearce, F.L.; Befus, A.D.; Bienenstock, J. Mucosal mast cells. III. Effect of quercetin and other flavonoids on antigen-induced histamine secretion from rat intestinal mast cells. J. Allergy Clin. Immunol., 1984, 73(6), 819-823.
[http://dx.doi.org/10.1016/0091-6749(84)90453-6] [PMID: 6202731]
[47]
Park, H.J.; Lee, C.M.; Jung, I.D.; Lee, J.S.; Jeong, Y.i.; Chang, J.H.; Chun, S.H.; Kim, M.J.; Choi, I.W.; Ahn, S.C.; Shin, Y.K.; Yeom, S.R.; Park, Y.M. Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int. Immunopharmacol., 2009, 9(3), 261-267.
[http://dx.doi.org/10.1016/j.intimp.2008.10.021] [PMID: 19061976]
[48]
Mlcek, J.; Jurikova, T.; Skrovankova, S.; Sochor, J. Quercetin and its anti-allergic immune response. Molecules, 2016, 21(5), 1-15.
[http://dx.doi.org/10.3390/molecules21050623] [PMID: 27187333]
[49]
Kumar, R.; Vijayalakshmi, S.; Nadanasabapathi, S. Health benefits of quercetin. Def. Life Sci. J., 2017, 2(2), 142.
[http://dx.doi.org/10.14429/dlsj.2.11359]
[50]
Cai, X.; Fang, Z.; Dou, J.; Yu, A.; Zhai, G. Bioavailability of quercetin: Problems and promises. Curr. Med. Chem., 2013, 20(20), 2572-2582.
[http://dx.doi.org/10.2174/09298673113209990120] [PMID: 23514412]
[51]
Kasikci, M.B.; Bagdatlioglu, N. Bioavailability of quercetin. Special Issue Nutrition in Conference October 2016. Curr. Res. Nutr. Food Sci., 2016, 4, 146-151.
[52]
Justino, G.C.; Santos, M.R.; Canário, S.; Borges, C.; Florêncio, M.H.; Mira, L. Plasma quercetin metabolites: Structure-antioxidant activity relationships. Arch. Biochem. Biophys., 2004, 432(1), 109-121.
[http://dx.doi.org/10.1016/j.abb.2004.09.007] [PMID: 15519302]
[53]
Ghanem, A.S.; Ali, H.S.; El-Shanawany, S.M.; Ibrahim, E.S. Solubility and dissolution enhancement of quercetin via preparation of spray dried microstructured solid dispersions. Thaiphesatchasan, 2013, 37(1), 12-24.
[54]
De Mello Costa, A.R.; Marquiafável, F.S.; de Oliveira Lima Leite Vaz, M.M. Quercetin-PVP K25 solid dispersions: Preparation, thermal characterization and antioxidant activity. J. Therm. Anal. Calorim., 2011, 104(1), 273-278.
[http://dx.doi.org/10.1007/s10973-010-1083-3]
[55]
Li, B.; Konecke, S.; Harich, K.; Wegiel, L.; Taylor, L.S.; Edgar, K.J. Solid dispersion of quercetin in cellulose derivative matrices influences both solubility and stability. Carbohydr. Polym., 2013, 92(2), 2033-2040.
[http://dx.doi.org/10.1016/j.carbpol.2012.11.073] [PMID: 23399255]
[56]
Zhao, G.; Duan, J.; Xie, Y.; Lin, G.; Luo, H.; Li, G.; Yuan, X. Effects of solid dispersion and self-emulsifying formulations on the solubility, dissolution, permeability and pharmacokinetics of isorhamnetin, quercetin and kaempferol in total flavones of Hippophae rhamnoides L. Drug Dev. Ind. Pharm., 2013, 39(7), 1037-1045.
[http://dx.doi.org/10.3109/03639045.2012.699066] [PMID: 22757776]
[57]
Setyawan, D.; Fadhil, A.A.; Juwita, D.; Yusuf, H.; Sari, R. Enhancement of solubility and dissolution rate of quercetin with solid dispersion system formation using hydroxypropyl methyl cellulose matrix. Thaiphesatchasan, 2017, 41(3), 112-116.
[58]
Sri, K.V.; Kondaiah, A.; Ratna, J.V.; Annapurna, A. Preparation and characterization of quercetin and rutin cyclodextrin inclusion complexes. Drug Dev. Ind. Pharm., 2007, 33(3), 245-253.
[http://dx.doi.org/10.1080/03639040601150195] [PMID: 17454057]
[59]
Dias, K.; Nikolaou, S.; De Giovani, W.F. Synthesis and spectral investigation of Al(III) catechin/β-cyclodextrin and Al(III) quercetin/β-cyclodextrin inclusion compounds. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2008, 70(1), 154-161.
[http://dx.doi.org/10.1016/j.saa.2007.07.022] [PMID: 18054838]
[60]
Borghetti, G.S.; Lula, I.S.; Sinisterra, R.D.; Bassani, V.L. Quercetin/β-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture. AAPS PharmSciTech, 2009, 10(1), 235-242.
[http://dx.doi.org/10.1208/s12249-009-9196-3] [PMID: 19280349]
[61]
Singh, D.; Rawat, M.S.M.; Semalty, A.; Semalty, M. Quercetin-phospholipid complex: an amorphous pharmaceutical system in herbal drug delivery. Curr. Drug Discov. Technol., 2012, 9(1), 17-24.
[http://dx.doi.org/10.2174/157016312799304507] [PMID: 21644920]
[62]
Liu, M.; Dong, L.; Chen, A.; Zheng, Y.; Sun, D.; Wang, X.; Wang, B. Inclusion complexes of quercetin with three β-cyclodextrins derivatives at physiological pH: Spectroscopic study and antioxidant activity. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2013, 115, 854-860.
[http://dx.doi.org/10.1016/j.saa.2013.07.008] [PMID: 23892509]
[63]
Kaur, H.; Kaur, G. A critical appraisal of solubility enhancement techniques of polyphenols. J. Pharm., 2014, 2014.
[64]
Aytac, Z.; Kusku, S.I.; Durgun, E.; Uyar, T. Quercetin/β-cyclodextrin inclusion complex embedded nanofibres: Slow release and high solubility. Food Chem., 2016, 197(Pt A), 864-871.
[http://dx.doi.org/10.1016/j.foodchem.2015.11.051] [PMID: 26617028]
[65]
Lan, Q.; Di, D.; Wang, S.; Zhao, Q.; Gao, Y.; Chang, D. Chitosan-N-acetylcysteine modified HP-β-CD inclusion complex as a potential ocular delivery system for anti-cataract drug: Quercetin. J. Drug Deliv. Sci. Technol., 2020, 55, 101407.
[http://dx.doi.org/10.1016/j.jddst.2019.101407]
[66]
Mulholland, P.J.; Ferry, D.R.; Anderson, D.; Hussain, S.A.; Young, A.M.; Cook, J.E.; Hodgkin, E.; Seymour, L.W.; Kerr, D.J. Pre-clinical and clinical study of QC12, a water-soluble, pro-drug of quercetin. Ann. Oncol., 2001, 12(2), 245-248.
[http://dx.doi.org/10.1023/A:1008372017097] [PMID: 11300332]
[67]
Jornada, D.H.; dos Santos Fernandes, G.F.; Chiba, D.E.; de Melo, T.R.; dos Santos, J.L.; Chung, M.C. The pro-drug approach: A successful tool for improving drug solubility. Molecules, 2015, 21(1), 42.
[http://dx.doi.org/10.3390/molecules21010042] [PMID: 26729077]
[68]
Tran, T.H.; Guo, Y.; Song, D.; Bruno, R.S.; Lu, X. Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. J. Pharm. Sci., 2014, 103(3), 840-852.
[http://dx.doi.org/10.1002/jps.23858] [PMID: 24464737]
[69]
Gonçalves, V.S.S.; Paz, E.; De Mato, C.; Martín, Á.; Cocero, M.J. Production of water soluble quercetin formulations by pressurized ethyl acetate-in-water emulsion technique using natural origin surfactants. Foodhyd, 2015, 51, 295-304.
[70]
Pangeni, R.; Kang, S.; Oak, M.; Park, E.Y.; Park, J.W. Oral delivery of quercetin in oil-in-water nanoemulsion: In vitro characterization and in vivo anti-obesity efficacy in mice. J. Funct. Foods, 2017, 38, 571-581.
[http://dx.doi.org/10.1016/j.jff.2017.09.059]
[71]
Chen, X.; McClements, D.J.; Zhu, Y.; Chen, Y. Enhancement of the solubility, stability and bioaccessibility of quercetin using protein-based excipient emulsions. Foodres, 2018, 114, 30-37.
[72]
Arbain, N.H.; Basri, M.; Salim, N.; Wui, W.T.; Rahman, M.A. Development and characterization of aerosol nanoemulsion system encapsulating low water soluble quercetin for lung. Mater. Today Proc., 2018, 5, S137-S142.
[http://dx.doi.org/10.1016/j.matpr.2018.08.055]
[73]
Iqbal, R.; Mehmood, Z.; Baig, A.; Khalid, N. Formulation and characterization of food grade O/W nanoemulsion encapsulating quercetin and curcumin: Insights on enhancing solubility characteristics. Food Bioprod. Process., 2020, 123, 304-311.
[http://dx.doi.org/10.1016/j.fbp.2020.07.013]
[74]
Dian, L.; Yu, E.; Chen, X.; Wen, X.; Zhang, Z.; Qin, L.; Wang, Q.; Li, G.; Wu, C. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles. Nanoscale Res. Lett., 2014, 9(1), 2406.
[http://dx.doi.org/10.1186/1556-276X-9-684] [PMID: 26088982]
[75]
Khonkarn, R.; Mankhetkorn, S.; Hennink, W.E.; Okonogi, S. PEG-OCL micelles for quercetin solubilization and inhibition of cancer cell growth. Eur. J. Pharm. Biopharm., 2011, 79(2), 268-275.
[http://dx.doi.org/10.1016/j.ejpb.2011.04.011] [PMID: 21596135]
[76]
Hassanzadeh, S.; Khoee, S.; Beheshti, A.; Hakkarainen, M. Release of quercetin from micellar nanoparticles with saturated and unsaturated core forming polyesters-a combined computational and experimental study. Mater. Sci. Eng. C, 2015, 46, 417-426.
[http://dx.doi.org/10.1016/j.msec.2014.10.059] [PMID: 25492006]
[77]
Chen, L.C.; Chen, Y.C.; Su, C.Y.; Hong, C.S.; Ho, H.O.; Sheu, M.T. Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study. Int. J. Nanomedi, 2016, 11, 1557-1566.
[PMID: 27143878]
[78]
Patra, A.; Satpathy, S.; Shenoy, A.K.; Bush, J.A.; Kazi, M.; Hussain, M.D. Formulation and evaluation of mixed polymeric micelles of quercetin for treatment of breast, ovarian, and multidrug resistant cancers. Int. J. Nanomedi, 2018, 13, 2869-2881.
[http://dx.doi.org/10.2147/IJN.S153094] [PMID: 29844670]
[79]
Singla, P.; Singh, O.; Chabba, S.; Mahajan, R.K. Pluronic-SAILs (Surface Active Ionic Liquids) mixed micelles as efficient hydrophobic quercetin drug carriers. J. Mol. Liq., 2018, 249, 294-303.
[http://dx.doi.org/10.1016/j.molliq.2017.11.044]
[80]
Mu, Y.; Fu, Y.; Li, J.; Yu, X.; Li, Y.; Wang, Y.; Wu, X.; Zhang, K.; Kong, M.; Feng, C.; Chen, X. Multifunctional quercetin conjugated chitosan nano-micelles with P-gp inhibition and permeation enhancement of anticancer drug. Carbohydr. Polym., 2019, 203, 10-18.
[http://dx.doi.org/10.1016/j.carbpol.2018.09.020] [PMID: 30318192]
[81]
Shen, F.; Zhong, H.; Ge, W.; Ren, J.; Wang, X. Quercetin/chitosan-graft-alpha lipoic acid micelles: A versatile antioxidant water dispersion with high stability. Carbohydr. Polym., 2020, 234, 115927.
[http://dx.doi.org/10.1016/j.carbpol.2020.115927] [PMID: 32070546]
[82]
Park, S.N.; Lee, M.H.; Kim, S.J.; Yu, E.R. Preparation of quercetin and rutin-loaded ceramide liposomes and drug-releasing effect in liposome-in-hydrogel complex system. Biochem. Biophys. Res. Commun., 2013, 435(3), 361-366.
[http://dx.doi.org/10.1016/j.bbrc.2013.04.093] [PMID: 23669037]
[83]
Jeon, S.; Yoo, C.Y.; Park, S.N. Improved stability and skin permeability of sodium hyaluronate-chitosan multilayered liposomes by Layer-by-Layer electrostatic deposition for quercetin delivery. Colloids Surf. B Biointerfaces, 2015, 129, 7-14.
[http://dx.doi.org/10.1016/j.colsurfb.2015.03.018] [PMID: 25819360]
[84]
Toniazzo, T.; Peres, M.S.; Paula, A.; Pinho, S.C. Encapsulation of quercetin in liposomes by ethanol injection and physicochemical characterization of dispersions and lyophilized vesicles. Food Biosci., 2017, 19, 17-25.
[http://dx.doi.org/10.1016/j.fbio.2017.05.003]
[85]
Seong, J.S.; Yun, M.E.; Park, S.N. Surfactant-stable and pH-sensitive liposomes coated with N-succinyl-chitosan and chitooligosaccharide for delivery of quercetin. Carbohydr. Polym., 2018, 181, 659-667.
[http://dx.doi.org/10.1016/j.carbpol.2017.11.098] [PMID: 29254020]
[86]
Caddeo, C.; Gabriele, M.; Fernàndez-Busquets, X.; Valenti, D.; Fadda, A.M.; Pucci, L.; Manconi, M. Antioxidant activity of quercetin in Eudragit-coated liposomes for intestinal delivery. Int. J. Pharm., 2019, 565, 64-69.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.007] [PMID: 31071415]
[87]
Chen, K.T.J.; Anantha, M.; Leung, A.W.Y.; Kulkarni, J.A.; Militao, G.G.C.; Wehbe, M.; Sutherland, B.; Cullis, P.R.; Bally, M.B. Characterization of a liposomal copper(II)-quercetin formulation suitable for parenteral use. Drug Deliv. Transl. Res., 2020, 10(1), 202-215.
[http://dx.doi.org/10.1007/s13346-019-00674-7] [PMID: 31482519]
[88]
Scarfato, P.; Avallone, E.; Iannelli, P.; Aquino, R.P.; Lauro, M.R.; Rossi, A. Quercetin microspheres by solvent evaporation : Preparation, characterization and release behavior. J. Appl. Polym. Sci., 2008, 109(5), 2994-3001.
[http://dx.doi.org/10.1002/app.28365]
[89]
Kim, Y.H.; Lee, D.W.; Jung, E.J. Preparation and characterization of quercetin-loaded silica microspheres stabilized by combined multiple emulsion and sol-gel processes. Chem. Ind. Chem. Eng. Q., 2015, 21(1), 85-94.
[http://dx.doi.org/10.2298/CICEQ131002010K]
[90]
Pathak, S.; Regmi, S.; Nguyen, T.T. Polymeric microsphere-facilitated site-specific delivery of quercetin prevents senescence of pancreatic islets in vivo and improves transplantation outcomes in mouse model of diabetes. Actbio, 2018, 75, 287-299.
[91]
Karthick, V.; Panda, S.; Kumar, V.G. Quercetin loaded PLGA microspheres induce apoptosis in breast cancer cells. Appl. Surf. Sci., 2019, 487, 211-217.
[http://dx.doi.org/10.1016/j.apsusc.2019.05.047]

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