Abstract
Flavonoids are the polyphenolic compounds widely found in plants, which possess several pharmacological activities such as, antioxidant, antinociceptive, anti-inflammatory, antiviral, antidiabetic and anticancer effects. Meanwhile, the aqueous solubility of these flavonoid compounds were very less which limits its oral administration also decreases the bioavailability and pharmacological activities. Recently, the cyclodextrin inclusion complexation method effectively improve the solubility and bioavailability of the flavonoids. The purpose of this review was to evaluate the bioavailability enhancement of flavonoid compounds after complexation with cyclodextrins. The search terms “flavonoids”, “pharmacokinetics”, “bioavailability” and “cyclodextrins” were used to retrieve the articles from, PubMed, Scopus and Web of Science until May 2018. 272 publications were identified and 20 studies were selected finally for the discussion of this review. From the selected studies the pharmacokinetic results reveal that the bioavailability of flavonoid compounds, complexed with cyclodextrins were extensively improved when compared to uncomplexed flavonoids, including the parameters such as, area under curve (AUC) and maximum plasma concentration (Cmax). The use of cyclodextrins can improve the oral bioavailability of flavonoids and it can also be a way to increase the therapeutic effects. Therefore, the incorporation of flavonoids in cyclodextrins increases the development of new pharmaceutical products for the clinical application.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Balasuriya N, Rupasinghe HPV (2012) Antihypertensive properties of flavonoid-rich apple peel extract. Food Chem 135:2320–2325. https://doi.org/10.1016/j.foodchem.2012.07.023
Campos CA, Lima BS, Trindade GGG et al (2019) Anti-hyperalgesic and anti-inflammatory effects of citral with β-cyclodextrin and hydroxypropyl-β-cyclodextrin inclusion complexes in animal models. Life Sci 229:139–148. https://doi.org/10.1016/j.lfs.2019.05.026
Carvalho YMBG, Menezes PP, Sousa BMH et al (2017) Inclusion complex between β-cyclodextrin and hecogenin acetate produces superior analgesic effect in animal models for orofacial pain. Biomed Pharmacother 93:754–762. https://doi.org/10.1016/J.BIOPHA.2017.06.091
Chanput W, Krueyos N, Ritthiruangdej P (2016) Anti-oxidative assays as markers for anti-inflammatory activity of flavonoids. Int Immunopharmacol 40:170–175. https://doi.org/10.1016/j.intimp.2016.08.038
Christodoulou E, Kechagia I-A, Tzimas S et al (2015) Serum and tissue pharmacokinetics of silibinin after per os and i.v. administration to mice as a HP-β-CD lyophilized product. Int J Pharm 493:366–373. https://doi.org/10.1016/j.ijpharm.2015.07.060
Del Valle EMM (2004) Cyclodextrins and their uses: a review. Process Biochem 39:1033–1046. https://doi.org/10.1016/S0032-9592(03)00258-9
Devasari N, Dora CP, Singh C et al (2015) Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: preparation, characterization, in silico, in vitro and in vivo evaluation. Carbohydr Polym 134:547–556. https://doi.org/10.1016/j.carbpol.2015.08.012
Dixit N, Baboota S, Kohli K et al (2007) Silymarin: a review of pharmacological aspects and bioavailability enhancement approaches. Indian J Pharmacol 39:172. https://doi.org/10.4103/0253-7613.36534
dos Menezes PP, Serafini MR, de Carvalho YMBG et al (2016) Kinetic and physical-chemical study of the inclusion complex of β-cyclodextrin containing carvacrol. J Mol Struct 1125:323–330. https://doi.org/10.1016/J.MOLSTRUC.2016.06.062
Duan S, Guan X, Lin R et al (2015) Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer’s disease. Neurobiol Aging 36:1792–1807. https://doi.org/10.1016/j.neurobiolaging.2015.02.002
Elhennawy MG, Lin H-S (2017) Quantification of apigenin trimethyl ether in rat plasma by liquid chromatography–tandem mass spectrometry: application to a pre-clinical pharmacokinetic study. J Pharm Biomed Anal 142:35–41. https://doi.org/10.1016/j.jpba.2017.03.070
Ferenci P, Scherzer T, Kerschner H et al (2008) Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 135:1561–1567. https://doi.org/10.1053/j.gastro.2008.07.072
Fernandes-Cunha GM, Gouvea DR, de Fulgêncio GO et al (2015) Development of a method to quantify clindamycin in vitreous humor of rabbits’ eyes by UPLC–MS/MS: application to a comparative pharmacokinetic study and in vivo ocular biocompatibility evaluation. J Pharm Biomed Anal 102:346–352. https://doi.org/10.1016/j.jpba.2014.08.023
Gazák R, Walterová D, Kren V (2007) Silybin and silymarin—new and emerging applications in medicine. Curr Med Chem 14:315–338
Gould S, Scott RC (2005) 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD): a toxicology review. Food Chem Toxicol 43:1451–1459. https://doi.org/10.1016/J.FCT.2005.03.007
Grzesik M, Naparło K, Bartosz G, Sadowska-Bartosz I (2018) Antioxidant properties of catechins: comparison with other antioxidants. Food Chem 241:480–492. https://doi.org/10.1016/j.foodchem.2017.08.117
Gutiérrez RMP, Baez EG (2009) Cardioactive agents from plants. Mini Rev Med Chem 9:878–899
Hawke RL, Schrieber SJ, Soule TA et al (2010) Silymarin ascending multiple oral dosing phase I study in noncirrhotic patients with chronic hepatitis C. J Clin Pharmacol 50:434–449. https://doi.org/10.1177/0091270009347475
Hodek P, Trefil P, Stiborová M (2002) Flavonoids-potent and versatile biologically active compounds interacting with cytochromes P450. Chem Biol Interact 139:1–21. https://doi.org/10.1016/S0009-2797(01)00285-X
Huang M, Chen W-J, Zhou Y et al (2013) Enantiomeric separations of four basic drugs containing N-alkyl groups by a RP-HPLC system using SBE-β-CD as chiral mobile phase additive. Chin Chem Lett 24:840–844. https://doi.org/10.1016/J.CCLET.2013.05.019
Huang Y, Zu Y, Zhao X et al (2016) Preparation of inclusion complex of apigenin-hydroxypropyl-β-cyclodextrin by using supercritical antisolvent process for dissolution and bioavailability enhancement. Int J Pharm 511:921–930. https://doi.org/10.1016/J.IJPHARM.2016.08.007
Iqbal J, Abbasi BA, Mahmood T et al (2017) Plant-derived anticancer agents: a green anticancer approach. Asian Pac J Trop Biomed 7:1129–1150. https://doi.org/10.1016/J.APJTB.2017.10.016
Jansook P, Ogawa N, Loftsson T (2018) Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. Int J Pharm 535:272–284. https://doi.org/10.1016/j.ijpharm.2017.11.018
Ju M-J, Yang D-H, Lee S-W et al (2007) Fabrication of TiO2/γ-CD films for nitro aromatic compounds and its sensing application via cyclic surface-polarization impedance (cSPI) spectroscopy. Sens Actuat B Chem 123:359–367. https://doi.org/10.1016/J.SNB.2006.08.035
Kadari A, Gudem S, Kulhari H et al (2017) Enhanced oral bioavailability and anticancer efficacy of fisetin by encapsulating as inclusion complex with HPβCD in polymeric nanoparticles. Drug Deliv 24:224–232. https://doi.org/10.1080/10717544.2016.1245366
Keshari AK, Kumar G, Kushwaha PS et al (2016) Isolated flavonoids from Ficus racemosa stem bark possess antidiabetic, hypolipidemic and protective effects in albino Wistar rats. J Ethnopharmacol 181:252–262. https://doi.org/10.1016/j.jep.2016.02.004
Kondeva-Burdina M, Shkondrov A, Simeonova R et al (2018) In vitro/in vivo antioxidant and hepatoprotective potential of defatted extract and flavonoids isolated from Astragalus spruneri Boiss. (Fabaceae). Food Chem Toxicol 111:631–640. https://doi.org/10.1016/j.fct.2017.12.020
Kubo M, Kimura Y, Odani T et al (1981) Studies on Scutellariae Radix. Planta Med 43:194–201. https://doi.org/10.1055/s-2007-971499
Kurkov SV, Loftsson T (2013) Cyclodextrins. Int J Pharm 453:167–180. https://doi.org/10.1016/j.ijpharm.2012.06.055
Lani R, Hassandarvish P, Shu M-H et al (2016) Antiviral activity of selected flavonoids against Chikungunya virus. Antivir Res 133:50–61. https://doi.org/10.1016/J.ANTIVIRAL.2016.07.009
Lee S-H, Kim YH, Yu H-J et al (2007) Enhanced bioavailability of soy isoflavones by complexation with β-cyclodextrin in rats. Biosci Biotechnol Biochem 71:2927–2933. https://doi.org/10.1271/bbb.70296
Li YC, Tyan YS, Kuo HM et al (2004) Baicalein induced in vitro apoptosis undergo caspases activity in human promyelocytic leukemia HL-60 cells. Food Chem Toxicol 42:37–43
Li J, Zhang M, Chao J, Shuang S (2009) Preparation and characterization of the inclusion complex of Baicalin (BG) with β-CD and HP-β-CD in solution: an antioxidant ability study. Spectrochim Acta Part A Mol Biomol Spectrosc 73:752–756. https://doi.org/10.1016/j.saa.2009.03.025
Li J, Jiang Q, Deng P et al (2017) The formation of a host-guest inclusion complex system between β-cyclodextrin and baicalin and its dissolution characteristics. J Pharm Pharmacol 69:663–674. https://doi.org/10.1111/jphp.12708
Lima PSS, Lucchese AM, Araújo-Filho HG et al (2016) Inclusion of terpenes in cyclodextrins: preparation, characterization and pharmacological approaches. Carbohydr Polym 151:965–987. https://doi.org/10.1016/J.CARBPOL.2016.06.040
Liu RH (2013) Health-promoting components of fruits and vegetables in the diet. Adv Nutr Int Rev J 4:384S–392S. https://doi.org/10.3945/an.112.003517
Liu J, Qiu L, Gao J, Jin Y (2006) Preparation, characterization and in vivo evaluation of formulation of baicalein with hydroxypropyl-β-cyclodextrin. Int J Pharm 312:137–143. https://doi.org/10.1016/j.ijpharm.2006.01.011
Liu B, Li W, Zhao J et al (2013) Physicochemical characterisation of the supramolecular structure of luteolin/cyclodextrin inclusion complex. Food Chem 141:900–906. https://doi.org/10.1016/j.foodchem.2013.03.097
Lo FH, Mak NK, Leung KN (2007) Studies on the anti-tumor activities of the soy isoflavone daidzein on murine neuroblastoma cells. Biomed Pharmacother 61:591–595. https://doi.org/10.1016/j.biopha.2007.08.021
Luke DR, Tomaszewski K, Damle B, Schlamm HT (2010) Review of the basic and clinical pharmacology of sulfobutylether-β-cydodextrin (SBECD). J Pharm Sci 99:3291–3301. https://doi.org/10.1002/jps.22109
Lv D, Cheng X, Tang L, Jiang M (2017) The cardioprotective effect of total flavonoids on myocardial ischemia/reperfusion in rats. Biomed Pharmacother 88:277–284. https://doi.org/10.1016/j.biopha.2017.01.060
Ma Y, Zhao X, Li J, Shen Q (2012) The comparison of different daidzein-PLGA nanoparticles in increasing its oral bioavailability. Int J Nanomed 7:559–570. https://doi.org/10.2147/IJN.S27641
Marrazzo G, Bosco P, La Delia F et al (2011) Neuroprotective effect of silibinin in diabetic mice. Neurosci Lett 504:252–256. https://doi.org/10.1016/j.neulet.2011.09.041
Matsuzaki Y, Kurokawa N, Terai S et al (1996) Cell death induced by baicalein in human hepatocellular carcinoma cell lines. Jpn J Cancer Res 87:170–177
Mekjaruskul C, Yang Y-T, Leed MGD et al (2013) Novel formulation strategies for enhancing oral delivery of methoxyflavones in Kaempferia parviflora by SMEDDS or complexation with 2-hydroxypropyl-β-cyclodextrin. Int J Pharm 445:1–11. https://doi.org/10.1016/j.ijpharm.2013.01.052
Menezes P, Frank LA, Lima B et al (2017) Hesperetin-loaded lipid-core nanocapsules in polyamide: a new textile formulation for topical drug delivery. Int J Nanomed 12:2069–2079. https://doi.org/10.2147/IJN.S124564
Miyake K, Arima H, Hirayama F et al (2000) Improvement of solubility and oral bioavailability of rutin by complexation with 2-hydroxypropyl-β-cyclodextrin. Pharm Dev Technol 5:399–407. https://doi.org/10.1081/PDT-100100556
Miyoshi N, Wakao Y, Tomono S et al (2011) The enhancement of the oral bioavailability of γ-tocotrienol in mice by γ-cyclodextrin inclusion. J Nutr Biochem 22:1121–1126. https://doi.org/10.1016/j.jnutbio.2010.09.011
Mohan S, Nandhakumar L (2014) Role of various flavonoids: hypotheses on novel approach to treat diabetes. J Med Hypotheses Ideas 8:1–6. https://doi.org/10.1016/J.JMHI.2013.06.001
Morazzoni P, Montalbetti A, Malandrino S, Pifferi G (1993) Comparative pharmacokinetics of silipide and silymarin in rats. Eur J Drug Metab Pharmacokinet 18:289–297. https://doi.org/10.1007/BF03188811
Mura P (2014) Analytical techniques for characterization of cyclodextrin complexes in aqueous solution: a review. J Pharm Biomed Anal 101:238–250. https://doi.org/10.1016/j.jpba.2014.02.022
Pan H, Wang H-B, Yu Y-B et al (2017) A superior preparation method for daidzein-hydroxypropyl-β-cyclodextrin complexes with improved solubility and dissolution: supercritical fluid process. Acta Pharm 67:85–97. https://doi.org/10.1515/acph-2017-0005
Penalva R, González-Navarro CJ, Gamazo C et al (2017) Zein nanoparticles for oral delivery of quercetin: pharmacokinetic studies and preventive anti-inflammatory effects in a mouse model of endotoxemia. Nanomed Nanotechnol, Biol Med 13:103–110. https://doi.org/10.1016/J.NANO.2016.08.033
Pérez-Abril M, Lucas-Abellán C, Castillo-Sánchez J et al (2017) Systematic investigation and molecular modelling of complexation between several groups of flavonoids and HP-β-cyclodextrins. J Funct Foods 36:122–131. https://doi.org/10.1016/J.JFF.2017.06.052
Pinho E, Grootveld M, Soares G, Henriques M (2014) Cyclodextrins as encapsulation agents for plant bioactive compounds. Carbohydr Polym 101:121–135. https://doi.org/10.1016/j.carbpol.2013.08.078
Polachi N, Bai G, Li T et al (2016) Modulatory effects of silibinin in various cell signaling pathways against liver disorders and cancer—a comprehensive review. Eur J Med Chem 123:577–595. https://doi.org/10.1016/j.ejmech.2016.07.070
Qiu N, Cheng X, Wang G et al (2014) Inclusion complex of barbigerone with hydroxypropyl-β-cyclodextrin: preparation and in vitro evaluation. Carbohydr Polym 101:623–630. https://doi.org/10.1016/j.carbpol.2013.09.035
Radu C-D, Parteni O, Ochiuz L (2016) Applications of cyclodextrins in medical textiles—review. J Control Release 224:146–157. https://doi.org/10.1016/j.jconrel.2015.12.046
Raffa D, Maggio B, Raimondi MV et al (2017) Recent discoveries of anticancer flavonoids. Eur J Med Chem 142:213–228. https://doi.org/10.1016/j.ejmech.2017.07.034
Rauf A, Uddin G, Siddiqui BS et al (2016) Antinociceptive and anti-inflammatory activities of flavonoids isolated from Pistacia integerrima galls. Complement Ther Med 25:132–138. https://doi.org/10.1016/j.ctim.2016.02.002
Ren L, Zhou Y, Wei P et al (2014) Preparation and pharmacokinetic study of aprepitant-sulfobutyl ether-β-cyclodextrin complex. AAPS PharmSciTech 15:121–130. https://doi.org/10.1208/s12249-013-0044-0
Sangpheak W, Kicuntod J, Schuster R et al (2015) Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin. Beilstein J Org Chem 11:2763–2773. https://doi.org/10.3762/bjoc.11.297
Seleem D, Pardi V, Murata RM (2017) Review of flavonoids: a diverse group of natural compounds with anti-Candida albicans activity in vitro. Arch Oral Biol 76:76–83. https://doi.org/10.1016/j.archoralbio.2016.08.030
Seo DJ, Jeon SB, Oh H et al (2016) Comparison of the antiviral activity of flavonoids against murine norovirus and feline calicivirus. Food Control 60:25–30. https://doi.org/10.1016/J.FOODCONT.2015.07.023
Shao Z-H, Li C-Q, Vanden Hoek TL et al (1999) Extract from Scutellaria baicalensis Georgi attenuates oxidant stress in cardiomyocytes. J Mol Cell Cardiol 31:1885–1895. https://doi.org/10.1006/jmcc.1999.1021
Shimoda K, Hamada H (2010) Synthesis of β-maltooligosaccharides of glycitein and daidzein and their anti-oxidant and anti-allergic activities. Molecules 15:5153–5161. https://doi.org/10.3390/molecules15085153
Shimoda K, Sato N, Kobayashi T et al (2008) Glycosylation of daidzein by the Eucalyptus cell cultures. Phytochemistry 69:2303–2306. https://doi.org/10.1016/J.PHYTOCHEM.2008.05.024
Shulman M, Cohen M, Soto-Gutierrez A et al (2011) Enhancement of naringenin bioavailability by complexation with hydroxypropoyl-β-cyclodextrin. PLoS ONE 6:e18033. https://doi.org/10.1371/journal.pone.0018033
Skottová N, Krecman V (1998) Silymarin as a potential hypocholesterolaemic drug. Physiol Res 47:1–7
Terao K, Nakata D, Fukumi H et al (2006) Enhancement of oral bioavailability of coenzyme Q10 by complexation with γ-cyclodextrin in healthy adults. Nutr Res 26:503–508. https://doi.org/10.1016/J.NUTRES.2006.08.004
Theodosiou E, Purchartová K, Stamatis H et al (2014) Bioavailability of silymarin flavonolignans: drug formulations and biotransformation. Phytochem Rev 13:1–18. https://doi.org/10.1007/s11101-013-9285-5
Trindade GGG, Thrivikraman G, Menezes PP et al (2019) Carvacrol/β-cyclodextrin inclusion complex inhibits cell proliferation and migration of prostate cancer cells. Food Chem Toxicol 125:198–209. https://doi.org/10.1016/j.fct.2019.01.003
Uchida R, Iwamoto K, Nagayama S et al (2015) Effect of γ-cyclodextrin inclusion complex on the absorption of R-α-lipoic acid in rats. Int J Mol Sci 16:10105–10120. https://doi.org/10.3390/ijms160510105
Voinovich D, Perissutti B, Grassi M et al (2009) Solid state mechanochemical activation of silybum marianum dry extract with betacyclodextrins: characterization and bioavailability of the coground systems. J Pharm Sci 98:4119–4129. https://doi.org/10.1002/jps.21704
Wang J, Cao Y, Sun B, Wang C (2011) Physicochemical and release characterisation of garlic oil-β-cyclodextrin inclusion complexes. Food Chem 127:1680–1685. https://doi.org/10.1016/j.foodchem.2011.02.036
Wang Y, Chen P, Tang C et al (2014) Antinociceptive and anti-inflammatory activities of extract and two isolated flavonoids of Carthamus tinctorius L. J Ethnopharmacol 151:944–950. https://doi.org/10.1016/j.jep.2013.12.003
Wang K, Lv Q, Miao Y et al (2018) Cardamonin, a natural flavone, alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway. Biochem Pharmacol 155:494–509. https://doi.org/10.1016/J.BCP.2018.07.039
Wei Y, Zhang J, Memon AH, Liang H (2017) Molecular model and in vitro antioxidant activity of a water-soluble and stable phloretin/hydroxypropyl-β-cyclodextrin inclusion complex. J Mol Liq 236:68–75. https://doi.org/10.1016/J.MOLLIQ.2017.03.098
Weyhenmeyer R, Mascher H, Birkmayer J (1992) Study on dose-linearity of the pharmacokinetics of silibinin diastereomers using a new stereospecific assay. Int J Clin Pharmacol Ther Toxicol 30:134–138
Wu JA, Attele AS, Zhang L, Yuan C-S (2001) Anti-HIV activity of medicinal herbs: usage and potential development. Am J Chin Med 29:69–81. https://doi.org/10.1142/S0192415X01000083
Wu J-W, Lin L-C, Hung S-C, Chi C-W, Tsai T-H (2007) Analysis of silibinin in rat plasma and bile for hepatobiliary excretion and oral bioavailability application. J Pharm Biomed Anal 45:635–641. https://doi.org/10.1016/j.jpba.2007.06.026
Wu W, Zu Y, Zhao X et al (2017) Solubility and dissolution rate improvement of the inclusion complex of apigenin with 2-hydroxypropyl-β-cyclodextrin prepared using the liquid antisolvent precipitation and solvent removal combination methods. Drug Dev Ind Pharm 43:1366–1377. https://doi.org/10.1080/03639045.2017.1318900
Xi J, Qian D, Duan J et al (2015) Preparation, characterization and pharmacokinetic study of Xiangfu Siwu decoction essential oil/β-cyclodextrin inclusion complex. Molecules 20:10705–10720. https://doi.org/10.3390/molecules200610705
Xie J, Yang F, Shi X et al (2013) Improvement in solubility and bioavailability of puerarin by mechanochemical preparation. Drug Dev Ind Pharm 39:826–835. https://doi.org/10.3109/03639045.2012.664147
Yang L-J, Ma S-X, Zhou S-Y et al (2013) Preparation and characterization of inclusion complexes of naringenin with β-cyclodextrin or its derivative. Carbohydr Polym 98:861–869. https://doi.org/10.1016/j.carbpol.2013.07.010
Yang X, Miao X, Cao F et al (2014) Nanosuspension development of scutellarein as an Active and rapid orally absorbed precursor of its BCS class IV Glycoside scutellarin. J Pharm Sci 103:3576–3584. https://doi.org/10.1002/jps.24149
Yang L-J, Xia S, Ma S-X et al (2016) Host–guest system of hesperetin and β-cyclodextrin or its derivatives: preparation, characterization, inclusion mode, solubilization and stability. Mater Sci Eng, C 59:1016–1024. https://doi.org/10.1016/j.msec.2015.10.037
Yao Y, Xie Y, Hong C et al (2014) Development of a myricetin/hydroxypropyl-β-cyclodextrin inclusion complex: preparation, characterization, and evaluation. Carbohydr Polym 110:329–337. https://doi.org/10.1016/j.carbpol.2014.04.006
Zeinali M, Rezaee SA, Hosseinzadeh H (2017) An overview on immunoregulatory and anti-inflammatory properties of chrysin and flavonoids substances. Biomed Pharmacother 92:998–1009. https://doi.org/10.1016/j.biopha.2017.06.003
Zhang L, Zhang J, Wang L, Xia H (2009) Ocular pharmacokinetics and availability of topically applied baicalein in rabbits. Curr Eye Res 34(4):257–263. https://doi.org/10.1080/02713680902725962
Zhang L, Lou J, Hu W et al (2014) Optimization and evaluation of a thermoresponsive ophthalmic in situ gel containing curcumin-loaded albumin nanoparticles. Int J Nanomed 9:2517. https://doi.org/10.2147/IJN.S60270
Zhang P, Liu X, Hu W et al (2016) Preparation and evaluation of naringenin-loaded sulfobutylether-β-cyclodextrin/chitosan nanoparticles for ocular drug delivery. Carbohydr Polym 149:224–230. https://doi.org/10.1016/j.carbpol.2016.04.115
Zhu H-J, Brinda BJ, Chavin KD et al (2013) An assessment of pharmacokinetics and antioxidant activity of free silymarin flavonolignans in healthy volunteers: a dose escalation study. Drug Metab Dispos 41:1679–1685. https://doi.org/10.1124/dmd.113.052423
Zu Y, Wu W, Zhao X et al (2014) Enhancement of solubility, antioxidant ability and bioavailability of taxifolin nanoparticles by liquid antisolvent precipitation technique. Int J Pharm 471:366–376. https://doi.org/10.1016/j.ijpharm.2014.05.049
Acknowledgements
This study was financed in part by the Conselho Nacional de Desenvolvimento Científico e Tecnológico—Brasil (CNPq), the Fundação de Apoio à Pesquisa e a Inovação Tecnológica do Estado de Sergipe (Fapitec/SE)—Brasil, the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES—Finance Code 001), and the Financiadora de Estudos e Projetos—Brasil (FINEP).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Figure 3
Flow diagram for study selection (DOCX 194 kb)
Rights and permissions
About this article
Cite this article
dos Santos Lima, B., Shanmugam, S., de Souza Siqueira Quintans, J. et al. Inclusion complex with cyclodextrins enhances the bioavailability of flavonoid compounds: a systematic review. Phytochem Rev 18, 1337–1359 (2019). https://doi.org/10.1007/s11101-019-09650-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11101-019-09650-y