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Environmental Chemistry Letters

, Volume 17, Issue 3, pp 1263–1270 | Cite as

Cyclodextrin-based delivery systems for dietary pharmaceuticals

  • Divya Arora
  • Ankit Saneja
  • Sundeep JaglanEmail author
Review
  • 122 Downloads

Abstract

The food industry is increasingly seeking innovative solutions for enhancing the bioavailability and clinical efficacy of phytochemicals. In this regard, cyclodextrins have gained widespread attention as functional excipients. Numerous studies have demonstrated that cyclodextrin inclusion complexes enhance the apparent water solubility, physical chemical stability, and improve the bioavailability of dietary phytochemicals. Recently, the dual-encapsulation approach has been developed, which involves the complexation of dietary molecules with cyclodextrins, followed by encapsulation into nanomaterials such as liposomes, nanoparticles and conjugates. Here, we review the current applications of natural and chemically modified cyclodextrins for the delivery of dietary phytochemicals. The main emphasis is given on inclusion complexes for enhancing the solubility, bioavailability and efficacy of dietary phytochemicals. We also discuss dual-encapsulation-based approaches developed for improved efficacy of dietary phytochemicals.

Keywords

Cyclodextrins Hydroxypropyl-β-cyclodextrin Drug delivery Nanoparticles 

Notes

Acknowledgements

S.J. thanks the Department of Science & Technology (DST), Government of India for financial assistance via Grant No. ECR/ 2017/001381. The manuscript bears institutional communication number IIIM/2279/2019.

References

  1. Abu-Dahab R, Odeh F, Ismail S, Azzam H, Al Bawab A (2013) Preparation, characterization and antiproliferative activity of thymoquinone-β-cyclodextrin self assembling nanoparticles. Die Pharmazie Int J Pharm Sci 68(12):939–944Google Scholar
  2. Alarcon De La Lastra C, Villegas I (2005) Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications. Mol Nutr Food Res 49(5):405–430CrossRefGoogle Scholar
  3. Al-Rawashdeh NA, Al-Sadeh KS, Al-Bitar M-B (2010) Physicochemical study on microencapsulation of hydroxypropyl-β-cyclodextrin in dermal preparations. Drug Dev Ind Pharm 36(6):688–697CrossRefGoogle Scholar
  4. Aqil F, Munagala R, Jeyabalan J, Vadhanam MV (2013) Bioavailability of phytochemicals and its enhancement by drug delivery systems. Cancer Lett 334(1):133–141CrossRefGoogle Scholar
  5. Arora D, Jaglan S (2016) Nanocarriers based delivery of nutraceuticals for cancer prevention and treatment: a review of recent research developments. Trends Food Sci Technol 54:114–126CrossRefGoogle Scholar
  6. Arora D, Jaglan S (2017) Therapeutic applications of resveratrol nanoformulations. Environ Chem Lett 16:35–41CrossRefGoogle Scholar
  7. Arora D, Saneja A, Jaglan S (2018) Cyclodextrin-based carriers for delivery of dietary phytochemicals. In: Fourmentin S et al. (ed) Cyclodextrin applications in medicine, food, environment and liquid crystals, pp 1–17.  https://doi.org/10.1007/978-3-319-76162-6_1
  8. Ashwaq AAS, Rasedee A, Abdul AB, Taufiq-Yap YH, Al-Qubaisi MS, Eid EE (2017) Characterization, drug release profile and cytotoxicity of dentatin-hydroxypropyl-β-cyclodextrin complex. J Incl Phenom Macrocycl Chem 87:167–178CrossRefGoogle Scholar
  9. Astray G, Gonzalez-Barreiro C, Mejuto J, Rial-Otero R, Simal-Gándara J (2009) A review on the use of cyclodextrins in foods. Food Hydrocoll 23(7):1631–1640CrossRefGoogle Scholar
  10. Avallone R, Zanoli P, Puia G, Kleinschnitz M, Schreier P, Baraldi M (2000) Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol 59(11):1387–1394CrossRefGoogle Scholar
  11. Baek J-S, Cho C-W (2017) A multifunctional lipid nanoparticle for co-delivery of paclitaxel and curcumin for targeted delivery and enhanced cytotoxicity in multidrug resistant breast cancer cells. Oncotarget 8(18):30369CrossRefGoogle Scholar
  12. Borghetti GS, Lula IS, Sinisterra RD, Bassani VL (2009) Quercetin/β-cyclodextrin solid complexes prepared in aqueous solution followed by spray-drying or by physical mixture. AAPS PharmSciTech 10(1):235–242CrossRefGoogle Scholar
  13. Brewster ME, Loftsson T (2007) Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev 59(7):645–666CrossRefGoogle Scholar
  14. Challa R, Ahuja A, Ali J, Khar R (2005) Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 6(2):E329–E357CrossRefGoogle Scholar
  15. Chen J, Lu W-L, Gu W, Lu S-S, Chen Z-P, Cai B-C, Yang X-X (2014) Drug-in-cyclodextrin-in-liposomes: a promising delivery system for hydrophobic drugs. Expert Opin Drug Deliv 11(4):565–577CrossRefGoogle Scholar
  16. Cravotto G, Binello A, Baranelli E, Carraro P, Trotta F (2006) Cyclodextrins as food additives and in food processing. Curr Nutr Food Sci 2(4):343–350CrossRefGoogle Scholar
  17. de Oliveira MG, Guimarães AG, Araújo Adriano A, Quintans Jullyana S, Santos MR, Quintans-Júnior LJ (2015) Cyclodextrins: improving the therapeutic response of analgesic drugs: a patent review. Expert Opin Ther Pat 25(8):897–907CrossRefGoogle Scholar
  18. di Cagno MP (2016) The potential of cyclodextrins as novel active pharmaceutical ingredients: a short overview. Molecules 22(1):1CrossRefGoogle Scholar
  19. Duarte A, Martinho A, Luís Â, Figueiras A, Oleastro M, Domingues FC, Silva F (2015) Resveratrol encapsulation with methyl-β-cyclodextrin for antibacterial and antioxidant delivery applications. LWT Food Sci Technol 63(2):1254–1260CrossRefGoogle Scholar
  20. Frémont L (2000) Biological effects of resveratrol. Life Sci 66(8):663–673CrossRefGoogle Scholar
  21. Gould S, Scott RC (2005) 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD): a toxicology review. Food Chem Toxicol 43(10):1451–1459CrossRefGoogle Scholar
  22. Hedges AR (1998) Industrial applications of cyclodextrins. Chem Rev 98(5):2035–2044CrossRefGoogle Scholar
  23. Hirayama F, Uekama K (1999) Cyclodextrin-based controlled drug release system. Adv Drug Deliv Rev 36(1):125–141CrossRefGoogle Scholar
  24. Irie T, Uekama K (1997) Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J Pharm Sci 86(2):147–162CrossRefGoogle Scholar
  25. Jambhekar SS, Breen P (2016) Cyclodextrins in pharmaceutical formulations I: structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov Today 21(2):356–362CrossRefGoogle Scholar
  26. Ji Y, Shan S, He M, Chu C-C (2017) Inclusion complex from cyclodextrin-grafted hyaluronic acid and pseudo protein as biodegradable nano-delivery vehicle for gambogic acid. Acta Biomater 62:234–245CrossRefGoogle Scholar
  27. Jun SW, Kim M-S, Kim J-S, Park HJ, Lee S, Woo J-S, Hwang S-J (2007) Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. Eur J Pharm Biopharm 66(3):413–421CrossRefGoogle Scholar
  28. Kaur N, Garg T, Goyal AK, Rath G (2016) Formulation, optimization and evaluation of curcumin-β-cyclodextrin-loaded sponge for effective drug delivery in thermal burns chemotherapy. Drug Deliv 23(7):2245–2254Google Scholar
  29. Kellici TF, Ntountaniotis D, Leonis G, Chatziathanasiadou M, Chatzikonstantinou AV, Becker-Baldus J, Glaubitz C, Tzakos AG, Viras K, Chatzigeorgiou P (2015) Investigation of the interactions of silibinin with 2-hydroxypropyl-β-cyclodextrin through biophysical techniques and computational methods. Mol Pharm 12(3):954–965CrossRefGoogle Scholar
  30. Lee S-H, Kim YH, Yu H-J, Cho N-S, Kim T-H, Kim D-C, Chung C-B, Hwang Y-I, Kim KH (2007) Enhanced bioavailability of soy isoflavones by complexation with β-cyclodextrin in rats. Biosci Biotechnol Biochem 71(12):2927–2933CrossRefGoogle Scholar
  31. Li S, Purdy WC (1992) Cyclodextrins and their applications in analytical chemistry. Chem Rev 92(6):1457–1470CrossRefGoogle Scholar
  32. Liu RH (2013) Health-promoting components of fruits and vegetables in the diet. Adv Nutr Int Rev J 4(3):384S–392SCrossRefGoogle Scholar
  33. Loftsson T, Brewster ME (2012) Cyclodextrins as functional excipients: methods to enhance complexation efficiency. J Pharm Sci 101(9):3019–3032CrossRefGoogle Scholar
  34. Loftsson T, Duchêne D (2007) Cyclodextrins and their pharmaceutical applications. Int J Pharm 329(1):1–11CrossRefGoogle Scholar
  35. Loftsson T, Jarho P, Masson M, Järvinen T (2005) Cyclodextrins in drug delivery. Expert Opin Drug Deliv 2(2):335–351CrossRefGoogle Scholar
  36. Lu Z, Cheng B, Hu Y, Zhang Y, Zou G (2009) Complexation of resveratrol with cyclodextrins: solubility and antioxidant activity. Food Chem 113(1):17–20CrossRefGoogle Scholar
  37. Manach C, Hubert J, Llorach R, Scalbert A (2009) The complex links between dietary phytochemicals and human health deciphered by metabolomics. Mol Nutr Food Res 53(10):1303–1315CrossRefGoogle Scholar
  38. Mangolim CS, Moriwaki C, Nogueira AC, Sato F, Baesso ML, Neto AM, Matioli G (2014) Curcumin-β-cyclodextrin inclusion complex: stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chem 153:361–370CrossRefGoogle Scholar
  39. Marques HMC (2010) A review on cyclodextrin encapsulation of essential oils and volatiles. Flavour Fragr J 25(5):313–326CrossRefGoogle Scholar
  40. Martina K, Binello A, Lawson D, Jicsinszky L, Cravotto G (2013) Recent applications of cyclodextrins as food additives and in food processing. Curr Nutr Food Sci 9(3):167–179CrossRefGoogle Scholar
  41. McClements DJ, Li F, Xiao H (2015) The nutraceutical bioavailability classification scheme: classifying nutraceuticals according to factors limiting their oral bioavailability. Ann Rev Food Sci Technol 6:299–327CrossRefGoogle Scholar
  42. Mellet CO, Fernández JMG, Benito JM (2011) Cyclodextrin-based gene delivery systems. Chem Soc Rev 40(3):1586–1608CrossRefGoogle Scholar
  43. Meyer H, Bolarinwa A, Wolfram G, Linseisen J (2006) Bioavailability of apigenin from apiin-rich parsley in humans. Ann Nutr Metab 50(3):167–172CrossRefGoogle Scholar
  44. Mohtar N, Taylor KM, Sheikh K, Somavarapu S (2017) Design and development of dry powder sulfobutylether-β-cyclodextrin complex for pulmonary delivery of fisetin. Eur J Pharm Biopharm 113:1–10CrossRefGoogle Scholar
  45. Oommen E, Shenoy BD, Udupa N, Kamath R, Devi P (1999) Antitumour Efficacy of Cyclodextrin-complexed and niosome-encapsulated plumbagin in mice bearing melanoma B16F1. Pharm Pharmacol Commun 5(4):281–285CrossRefGoogle Scholar
  46. Oprean C, Mioc M, Csányi E, Ambrus R, Bojin F, Tatu C, Cristea M, Ivan A, Danciu C, Dehelean C (2016) Improvement of ursolic and oleanolic acids’ antitumor activity by complexation with hydrophilic cyclodextrins. Biomed Pharmacother 83:1095–1104CrossRefGoogle Scholar
  47. Pápay ZE, Sebestyén Z, Ludányi K, Kállai N, Balogh E, Kósa A, Somavarapu S, Böddi B, Antal I (2016) Comparative evaluation of the effect of cyclodextrins and pH on aqueous solubility of apigenin. J Pharm Biomed Anal 117:210–216CrossRefGoogle Scholar
  48. Pinho E, Grootveld M, Soares G, Henriques M (2014) Cyclodextrins as encapsulation agents for plant bioactive compounds. Carbohydr Polym 101:121–135CrossRefGoogle Scholar
  49. Pinho E, Soares G, Henriques M (2015) Cyclodextrin modulation of gallic acid in vitro antibacterial activity. J Incl Phenom Macrocycl Chem 81(1–2):205–214CrossRefGoogle Scholar
  50. Popat A, Karmakar S, Jambhrunkar S, Xu C, Yu C (2014) Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity. Colloids Surf B 117:520–527CrossRefGoogle Scholar
  51. Popović M, Kaurinović B, Trivić S, Mimica-Dukić N, Bursać M (2006) Effect of celery (Apium graveolens) extracts on some biochemical parameters of oxidative stress in mice treated with carbon tetrachloride. Phytother Res 20(7):531–537CrossRefGoogle Scholar
  52. Serri C, Argirò M, Piras L, Mita DG, Saija A, Mita L, Forte M, Giarra S, Biondi M, Crispi S (2017) Nano-precipitated curcumin loaded particles: effect of carrier size and drug complexation with (2-hydroxypropyl)-β-cyclodextrin on their biological performances. Int J Pharm 520(1):21–28CrossRefGoogle Scholar
  53. Shulman M, Cohen M, Soto-Gutierrez A, Yagi H, Wang H, Goldwasser J, Lee-Parsons CW, Benny-Ratsaby O, Yarmush ML, Nahmias Y (2011) Enhancement of naringenin bioavailability by complexation with hydroxypropoyl-β-cyclodextrin. PLoS ONE 6(4):e18033CrossRefGoogle Scholar
  54. Silva JC, Almeida JR, Quintans JS, Gopalsamy RG, Shanmugam S, Serafini MR, Oliveira MR, Silva BA, Martins AO, Castro FF (2016) Enhancement of orofacial antinociceptive effect of carvacrol, a monoterpene present in oregano and thyme oils, by β-cyclodextrin inclusion complex in mice. Biomed Pharmacother 84:454–461CrossRefGoogle Scholar
  55. Soica C, Danciu C, Savoiu-Balint G, Borcan F, Ambrus R, Zupko I, Bojin F, Coricovac D, Ciurlea S, Avram S (2014) Betulinic acid in complex with a gamma-cyclodextrin derivative decreases proliferation and in vivo tumor development of non-metastatic and metastatic B164A5 cells. Int J Mol Sci 15(5):8235–8255CrossRefGoogle Scholar
  56. Stella VJ, He Q (2008) Cyclodextrins. Toxicol Pathol 36(1):30–42CrossRefGoogle Scholar
  57. Suzuki R, Inoue Y, Tsunoda Y, Murata I, Isshiki Y, Kondo S, Kanamoto I (2015) Effect of γ-cyclodextrin derivative complexation on the physicochemical properties and antimicrobial activity of hinokitiol. J Incl Phenom Macrocycl Chem 83(1–2):177–186CrossRefGoogle Scholar
  58. Wang X, Deng L, Cai L, Zhang X, Zheng H, Deng C, Duan X, Zhao X, Wei Y, Chen L (2011) Preparation, characterization, pharmacokinetics, and bioactivity of honokiol-in-hydroxypropyl-β-cyclodextrin-in-liposome. J Pharm Sci 100(8):3357–3364CrossRefGoogle Scholar
  59. Wu H, Liang H, Yuan Q, Wang T, Yan X (2010) Preparation and stability investigation of the inclusion complex of sulforaphane with hydroxypropyl-β-cyclodextrin. Carbohydr Polym 82(3):613–617CrossRefGoogle Scholar
  60. Xu X, Yu H, Hang L, Shao Y, Ding S, Yang X (2014) Preparation of naringenin/β-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats. BioMed Res Int 2014:623509Google Scholar
  61. Yang L-J, Ma S-X, Zhou S-Y, Chen W, Yuan M-W, Yin Y-Q, Yang X-D (2013) Preparation and characterization of inclusion complexes of naringenin with β-cyclodextrin or its derivative. Carbohydr Polym 98(1):861–869CrossRefGoogle Scholar
  62. Yang Z, Argenziano M, Salamone P, Pirro E, Sprio AE, Di Scipio F, Carere ME, Quaglino E, Cavallo F, Cavalli R (2016) Preclinical pharmacokinetics comparison between resveratrol 2-hydroxypropyl-β-cyclodextrin complex and resveratrol suspension after oral administration. J Incl Phenom Macrocycl Chem 86(3–4):263–271CrossRefGoogle Scholar
  63. Yee EM, Hook JM, Bhadbhade MM, Vittorio O, Kuchel RP, Brandl MB, Tilley RD, Black DS, Kumar N (2017) Preparation, characterization and in vitro biological evaluation of (1:2) phenoxodiol-β-cyclodextrin complex. Carbohydr Polym 165:444–454CrossRefGoogle Scholar
  64. Zhang J, Ma PX (2013) Cyclodextrin-based supramolecular systems for drug delivery: recent progress and future perspective. Adv Drug Deliv Rev 65(9):1215–1233CrossRefGoogle Scholar
  65. Zhang L, Man S, Qiu H, Liu Z, Zhang M, Ma L, Gao W (2016) Curcumin-cyclodextrin complexes enhanced the anti-cancer effects of curcumin. Environ Toxicol Pharmacol 48:31–38CrossRefGoogle Scholar
  66. Zhu Z-Y, Luo Y, Liu Y, Wang X-T, Liu F, Guo M-Z, Wang Z, Liu A-J, Zhang Y-M (2016) Inclusion of chrysin in β-cyclodextrin and its biological activities. J Drug Deliv Sci Technol 31:176–186CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Microbial Biotechnology DivisionCSIR-Indian Institute of Integrative MedicineJammuIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR)JammuIndia
  3. 3.Product Development Cell-IINational Institute of ImmunologyNew DelhiIndia

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