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Pharmaceutical applications of cyclodextrins and their derivatives

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Abstract

Cyclodextrins (CDs) are abundantly explored in the field of medicines for the design of various types of drug delivery systems. They are cyclic oligosaccharides carrying α (1,4) glucopyranose units and able to build aqueous soluble inclusion complexes with various small and large drug molecules. These molecules have a unique structural feature and categorized into hydrophobic, hydrophilic and ionic derivatives. Villiers and Schardinger in 1891, first described the chemical nature and types of cyclodextrin. Cramer and co-workers in 1955 illustrated their latent to make water soluble inclusion complexes with various active components. These CDs molecules are used in pharmaceutical field practically and economically to improve the stability, solubility as well as bioavailability of drug molecules. In this review article physical characteristic, chemical nature and applications of different cyclodextrin and their derivatives in different drug delivery systems and toxicological effects are engrossed.

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References

  1. Dutta, R.C.: Drug carriers in pharmaceutical design: promises and progress. Curr. Pharm. Des. 13, 761–769 (2007)

    CAS  PubMed  Google Scholar 

  2. Ngwuluka, N.C., Ochekpe, N.A., Aruoma, O.I.: Naturapolyceutics: the science of utilizing natural polymers for drug delivery. Polymers. 6(5), 1312–1332 (2014)

    Google Scholar 

  3. Bhatia, M., Ahuja, M.: Psyllium arabinoxylan: carboxymethylation, characterization and evaluation for nanoparticulate drug delivery. Int. J. Biol. Macromol. 72, 495–501 (2015)

    CAS  PubMed  Google Scholar 

  4. Bhatia, M., Ahuja, M., Mehta, H.: Thiol derivatization of xanthan gum and its evaluation as a mucoadhesive polymer. Carbohydr. Polym. 131, 119–124 (2015)

    CAS  PubMed  Google Scholar 

  5. Ahuja, M., Bhatia, M., Saini, K.: Sodium alginate–arabinoxylan composite microbeads: preparation and characterization. J. Pharm. Invest. 46(7), 645–653 (2016)

    CAS  Google Scholar 

  6. Siemoneit, U., Schmitt, C., Alvarez-Lorenzo, C., Luzardo, A., Otero-Espinar, F., Concheiro, A., Blanco-Méndez, J.: Acrylic/cyclodextrin hydrogels with enhanced drug loading and sustained release capability. Int. J. Pharm. 312, 66–74 (2006)

    CAS  PubMed  Google Scholar 

  7. Liao, R., Lv, P., Wang, Q., Zheng, J., Feng, B., Yang, B.: Cyclodextrin-based biological stimuli-responsive carriers for smart and precision medicine. Biomater. Sci. 5, 1736–1745 (2017)

    CAS  PubMed  Google Scholar 

  8. Cui, X., Wang, N., Wang, H., Li, G., Tao, Q.: pH sensitive supramolecular vesicles from cyclodextrin graft copolymer and benzimidazole ended block copolymer as dual drug carriers. Int. J. Polym. Mater. Polym. Biomater. 68, 733–740 (2019)

    CAS  Google Scholar 

  9. Barse, B., Kaul, N., Banerjee, N., Kaul, C.L., Banerjee, U.: Cyclodextrins: emerging applications. Chim. Oggi 21, 48–54 (2003)

    CAS  Google Scholar 

  10. Hedges, A.R.: Industrial applications of cyclodextrins. Chem. Rev. 98, 2035–2044 (1998)

    CAS  PubMed  Google Scholar 

  11. Lu, X., Chen, Y.: Chiral separation of amino acids derivatized with fluoresceine-5-isothiocyanate by capillary electrophoresis and laser-induced fluorescence detection using mixed selectors of β-cyclodextrin and sodium taurocholate. J. Chromatogr. A 955, 133–140 (2002)

    CAS  PubMed  Google Scholar 

  12. Baudin, C., Pean, C., Perly, B., Gosselin, P.: Inclusion of organic pollutants in cyclodextrins and derivatives. Int. J. Environ. Anal. Chem. 77, 233–242 (2000)

    CAS  Google Scholar 

  13. Larson, S.B., Day, J.S., McPherson, A.: X-ray crystallographic analyses of pig pancreatic α-amylase with limit dextrin, oligosaccharide, and α-cyclodextrin. Biochemistry 49, 3101–3115 (2010)

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Higuchi, T.: A phase solubility technique. Adv. Anal. Chem. Instrum. 4, 117–211 (1965)

    CAS  Google Scholar 

  15. Cramer, F., Saenger, W., Spatz, H.C.: Inclusion compounds. XIX. 1a the formation of inclusion compounds of α-cyclodextrin in aqueous solutions. Thermodynamics and kinetics. J. Am. Chem. Soc. 89, 14–20 (1967)

    CAS  Google Scholar 

  16. Szejtli, J.: Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1754 (1998)

    CAS  PubMed  Google Scholar 

  17. Qi, Q., Zimmermann, W.: Cyclodextrin glucanotransferase: from gene to applications. Appl. Microbiol. Biotechnol. 66, 475–485 (2005)

    CAS  PubMed  Google Scholar 

  18. Qi, Q., Mokhtar, M.N., Zimmermann, W.: Effect of ethanol on the synthesis of large-ring cyclodextrins by cyclodextrin glucanotransferases. J. Incl. Phenom. Macrocycl. Chem. 57, 95–99 (2007)

    CAS  Google Scholar 

  19. Li, Z., Wang, M., Wang, F., Gu, Z., Du, G., Wu, J., Chen, J.: γ-Cyclodextrin: a review on enzymatic production and applications. Appl. Microbiol. Biotechnol. 77, 245 (2007)

    CAS  PubMed  Google Scholar 

  20. Lichtenthaler, F.W., Immel, S.: Cyclodextrins, cyclomannins, and cyclogalactins with five and six (1→ 4)-linked sugar units: a comparative assessment of their conformations and hydrophobicity potential profiles1. Tetrahedron Asymmetry 5, 2045–2060 (1994)

    CAS  Google Scholar 

  21. Saokham, P., Muankaew, C., Jansook, P., Loftsson, T.: Solubility of cyclodextrins and drug/cyclodextrin complexes. Molecules 23, 1161 (2018)

    PubMed Central  Google Scholar 

  22. Bai, L., Xu, X.M., He, J., Pan, S.Z.: Inclusion complexation, encapsulation interaction and inclusion number in cyclodextrin chemistry. Coord. Chem. Rev. 253, 1276–1284 (2009)

    Google Scholar 

  23. Szejtli, J.: Past, present and futute of cyclodextrin research. Pure Appl. Chem. 76, 1825–1845 (2007)

    Google Scholar 

  24. Li, S., Purdy, W.C.: Cyclodextrins and their applications in analytical chemistry. Chem. Rev. 92, 1457–1470 (1992)

    CAS  Google Scholar 

  25. Del Valle, E.M.: Cyclodextrins and their uses: a review. Process Biochem. 39, 1033–1046 (2004)

    Google Scholar 

  26. Loftsson, T., Fridriksdottir, H.: The effect of water-soluble polymers on the aqueous solubility and complexing abilities of β-cyclodextrin. Int. J. Pharm. 163, 115–121 (1998)

    CAS  Google Scholar 

  27. Szente, L., Szejtli, J.: Highly soluble cyclodextrin derivatives: chemistry, properties, and trends in development. Adv. Drug Deliv. Rev. 36, 17–28 (1996)

    Google Scholar 

  28. Dubes, A., Degobert, G., Fessi, H., Parrot-Lopez, H.: Synthesis and characterisation of sulfated amphiphilic α-, β-and γ-cyclodextrins: application to the complexation of acyclovir. Carbohydr. Res. 338, 2185–2193 (2003)

    CAS  PubMed  Google Scholar 

  29. Yamamoto, M., Yoshida, A., Hirayama, F., Uekama, K.: Some physicochemical properties of branched β-cyclodextrins and their inclusion characteristics. Int. J. Pharm. 49, 163–171 (1989)

    CAS  Google Scholar 

  30. Sakuraba, H., Natori, K., Tanaka, Y.: Asymmetric oxidation of alkyl aryl sulfides in crystalline cyclodextrin complexes. J. Org. Chem. 56, 4124–4129 (1991)

    CAS  Google Scholar 

  31. Pitha, J., Milecki, J., Fales, H., Pannell, L., Uekama, K.: Hydroxypropyl-β-cyclodextrin: preparation and characterization; effects on solubility of drugs. Int. J. Pharm. 29, 73–82 (1986)

    CAS  Google Scholar 

  32. Uekama, K., Hirayama, F., Irie, T.: Cyclodextrin drug carrier systems. Chem. Rev. 98, 2045–2076 (1998)

    CAS  PubMed  Google Scholar 

  33. Memisoglu, B., Erem, A., Bochot, L., Trichard, D., Duchene, Hıncal, A.A.: Amphiphilic cyclodextrins and microencapsulation. In: Microencapsulation, 2nd Edn. 270 Madison Avenue New York (2005)

  34. Auzely-Velty, R., Djedaini-Pilard, F., Desert, S., Perly, B., Zemb, T.: Micellization of hydrophobically modified cyclodextrins. 1. Micellar structure. Langmuir 16, 3727–3734 (2000)

    CAS  Google Scholar 

  35. Sukegawa, T., Furuike, T., Niikura, K., Yamagishi, A., Monde, K., Nishimura, S.I.: Erythrocyte-like liposomes prepared by means of amphiphilic cyclodextrin sulfates. Chem. Commun. 5, 430–431 (2002)

    Google Scholar 

  36. Chen, X., Qiu, Y.K., Owh, C., Loh, X.J., Wu, Y.L.: Supramolecular cyclodextrin nanocarriers for chemo-and gene therapy towards the effective treatment of drug resistant cancers. Nanoscale. 8, 18876–18881 (2016)

    CAS  PubMed  Google Scholar 

  37. Zhang, P., Chang-Chun, L., Coleman, A.W., Parrot-Lopez, H., Galons, H.: Formation of amphiphilic cyclodextrins via hydrophobic esterification at the secondary hydroxyl face. Tetrahedron Lett. 32, 2769–2770 (1991)

    CAS  Google Scholar 

  38. Canceill, J., Jullien, L., Lacombe, L., Lehn, J.M.: Channel-type molecular structures. Part 2. Synthesis of bouquet-shaped molecules based on a β-cyclodextrin core. Helv. Chim. Acta 75, 791–812 (1992)

    CAS  Google Scholar 

  39. Bellanger, N., Perly, B.: NMR investigations of the conformation of new cyclodextrin-based amphiphilic transporters for hydrophobic drugs: molecular lollipops. J. Mol. Struct. 273, 215–226 (1992)

    CAS  Google Scholar 

  40. Koehler, J.E.H., Saenger, W., Van Gunsteren, W.F.: Conformational differences between α-cyclodextrin in aqueous solution and in crystalline form: a molecular dynamics study. J. Mol. Biol. 203, 241–250 (1988)

    CAS  PubMed  Google Scholar 

  41. Renard, E., Deratani, A., Volet, G., Sebille, B.: Preparation and characterization of water soluble high molecular weight β-cyclodextrin-epichlorohydrin polymers. Eur. Polym. J. 33, 49–57 (1997)

    CAS  Google Scholar 

  42. Cadars, S., Foray, M.F., Gadelle, A., Gerbaud, G., Bardet, M.: High-resolution solid-state 13C NMR study of per (3, 6-anhydro)-α-cyclodextrin based polymers and of their chromium complexes. Carbohydr. Polym. 61, 88–94 (2005)

    CAS  Google Scholar 

  43. Zhao, D., Zhao, L., Zhu, C.S., Huang, W.Q., Hu, J.L.: Water-insoluble β-cyclodextrin polymer crosslinked by citric acid: synthesis and adsorption properties toward phenol and methylene blue. J. Incl. Phenom. Macrocycl. Chem. 63, 195–201 (2009)

    CAS  Google Scholar 

  44. Girek, T., Kozlowski, C.A., Koziol, J.J., Walkowiak, W., Korus, I.: Polymerisation of β-cyclodextrin with succinic anhydride. Synthesis, characterisation, and ion flotation of transition metals. Carbohydr. Polym. 59, 211–215 (2005)

    CAS  Google Scholar 

  45. De Brauer, C., Merlin, M.P., Germain, P., Guerandel, T.: Thermal behaviour of anhydrous α-, β-and γ-cyclodextrin at low temperature. J. Incl. Phenom. Macrocycl. Chem. 37(1–4), 75–82 (2000)

    Google Scholar 

  46. Giordano, F., Novak, C., Moyano, J.R.: Thermal analysis of cyclodextrins and their inclusion compounds. Thermochim. Acta 380, 123–151 (2001)

    CAS  Google Scholar 

  47. Ritter, H., Tabatabai, M.: Cyclodextrin in polymer synthesis: a green way to polymers. Prog. Polym. Sci. 9, 1713–1720 (2002)

    Google Scholar 

  48. Loftsson, T., Brewster, M.E.: Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J. Pharm. Sci. 85, 1017–1025 (1996)

    CAS  PubMed  Google Scholar 

  49. Tomasik, P.: Complexes of starch with inorganic guests. Adv. Carbohydr. Chem. Biochem. 53, 263–343 (1996)

    Google Scholar 

  50. Aoyama, Y., Nagai, Y., Otsuki, J.I., Kobayashi, K., Toi, H.: Selective binding of sugar to β-cyclodextrin: a prototype for sugar–sugar interactions in water. Angew. Chem. Int. Ed. Engl. 31, 745–747 (1992)

    Google Scholar 

  51. Gabelica, V., Galic, N., De Pauw, E.: On the specificity of cyclodextrin complexes detected by electrospray mass spectrometry. J. Am. Soc. Mass Spectrom. 13, 946–953 (2002)

    CAS  PubMed  Google Scholar 

  52. Loftsson, T., Magnusdottir, A., Masson, M., Sigurjonsdottir, J.F.: Self-association and cyclodextrin solubilization of drugs. J. Pharm. Sci. 91, 2307–2316 (2002)

    CAS  PubMed  Google Scholar 

  53. Mura, P.: Analytical techniques for characterization of cyclodextrin complexes in aqueous solution: a review. J. Pharm. Biomed. Anal. 101, 238–250 (2014)

    CAS  PubMed  Google Scholar 

  54. Lai, H., Zhao, T., Deng, Y., Fan, C., Wu, W., Yang, C.: Assembly-enhanced triplet-triplet annihilation upconversion in the aggregation formed by Schiff-base Pt (II) complex grafting-permethyl-β-CD and 9, 10-diphenylanthracence dimer. Chin. Chem. Lett. 30, 1979–1983 (2019)

    CAS  Google Scholar 

  55. Liu, R., Zhang, Y., Wu, W., Liang, W., Huang, Q., Yu, X., Xu, W., Zhou, D., Selvapalam, N., Yang, C.: Temperature-driven braking of γ-cyclodextrin-curcubit [6] uril-cowheeled [4] rotaxanes. Chin. Chem. Lett. 30, 577–581 (2019)

    CAS  Google Scholar 

  56. Xu, J., Wang, Q., Xuan, C., **a, Q., Lin, X., Fu, Y.: Chiral recognition of tryptophan enantiomers based on β-cyclodextrin-platinum nanoparticles/graphene nanohybrids modified electrode. Electroanalysis 28(4), 868–873 (2016)

    CAS  Google Scholar 

  57. Prentis, R.A., Lis, Y., Walker, S.R.: Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964–1985). Br. J. Clin. Pharmacol. 25, 387–396 (1988)

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Dressman, J.B., Amidon, G.L., Reppas, C., Shah, V.P.: Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms. Pharm. Res. 15, 11–22 (1998)

    CAS  PubMed  Google Scholar 

  59. Ahr, G., Voith, B., Kuhlmann, J.: Guidances related to bioavailability and bioequivalence: European industry perspective. Eur. J. Drug Metab. Pharmacokinet. 25, 25–27 (2000)

    CAS  PubMed  Google Scholar 

  60. Davis, M.E., Brewster, M.E.: Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov. 3, 1023 (2004)

    CAS  PubMed  Google Scholar 

  61. Dressman, J., Butler, J., Hempenstall, J., Reppas, C.: The BCS: where do we go from here? Pharm. Tech. 25, 68–76 (2001)

    CAS  Google Scholar 

  62. Strickley, R.G.: Solubilizing excipients in oral and injectable formulations. Pharm. Res. 21, 201–230 (2004)

    CAS  PubMed  Google Scholar 

  63. Kurkov, S.V., Loftsson, T.: Cyclodextrins. Int. J. Pharm. 453, 167–180 (2013)

    CAS  PubMed  Google Scholar 

  64. Adeoye, O., Cabral-Marques, H.: Cyclodextrin nanosystems in oral drug delivery: a mini review. Int. J. Pharm. 531, 521–531 (2017)

    CAS  PubMed  Google Scholar 

  65. Loftsson, T., Matthiasson, K., Masson, M.: The effects of organic salts on the cyclodextrin solubilization of drugs. Int. J. Pharm. 262, 101–107 (2003)

    CAS  PubMed  Google Scholar 

  66. Lantz, A.W., Rodriguez, M.A., Wetterer, S.M., Armstrong, D.W.: Estimation of association constants between oral malodor components and various native and derivatized cyclodextrins. Anal. Chim. Acta 557, 184–190 (2006)

    CAS  Google Scholar 

  67. Szejtli, J., Szente, L.: Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur. J. Pharm. Biopharm. 61, 115–125 (2005)

    CAS  PubMed  Google Scholar 

  68. Vyas, A., Saraf, S., Saraf, S.: Cyclodextrin based novel drug delivery systems. J. Incl. Phenom. Macrocycl. Chem. 62, 23–42 (2008)

    CAS  Google Scholar 

  69. Soares, A.F., Carvalho, R.D.A., Veiga, F.: Oral administration of peptides and proteins: nanoparticles and cyclodextrins as biocompatible delivery systems. Nanomedicine (2007). https://doi.org/10.2217/17435889.2.2.183

    Article  PubMed  Google Scholar 

  70. Stella, V.J., He, Q.: Cyclodextrins. Toxicol Pathol. 36, 30–42 (2008)

    CAS  PubMed  Google Scholar 

  71. Shimpi, S., Chauhan, B., Shimpi, P.: Cyclodextrins: application in different routes of drug administration. Acta Pharm. 55, 139–156 (2005)

    CAS  PubMed  Google Scholar 

  72. Liversidge, G.G., Cundy, K.C.: Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int. J. Pharm. 125, 91–97 (1995)

    CAS  Google Scholar 

  73. Haeberlin, B., Gengenbacher, T., Meinzer, A., Fricker, G.: Cyclodextrins—useful excipients for oral peptide administration? Int. J. Pharm. 137, 103–110 (1996)

    CAS  Google Scholar 

  74. Veiga, F., Teixeira-Dias, J.J.C., Kedzierewicz, F., Sousa, A., Maincent, P.: Inclusion complexation of tolbutamide with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Int. J. Pharm. 129, 63–71 (1996)

    CAS  Google Scholar 

  75. Glasmacher, A., Hahn, C., Molitor, E., Marklein, G., Sauerbruch, T., Schmidt-Wolf, I.G.H.: Itraconazole trough concentrations in antifungal prophylaxis with six different dosing regimens using hydroxypropyl-β-cyclodextrin oral solution or coated-pellet capsules. Mycoses 42, 591–600 (1999)

    CAS  PubMed  Google Scholar 

  76. Ozkan, Y., Atay, T., Dikmen, N., Isimer, A., Aboul-Enein, H.Y.: Improvement of water solubility and in vitro dissolution rate of gliclazide by complexation with β-cyclodextrin. Pharm. Acta Helv. 74, 365–370 (2000)

    CAS  PubMed  Google Scholar 

  77. Patel, S.G., Rajput, S.J.: Enhancement of oral bioavailability of cilostazol by forming its inclusion complexes. AAPS PharmSciTech. 10, 660–669 (2009)

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Miro, A., Rondinone, A., Nappi, A., Ungaro, F., Quaglia, F., La Rotonda, M.I.: Modulation of release rate and barrier transport of Diclofenac incorporated in hydrophilic matrices: role of cyclodextrins and implications in oral drug delivery. Eur. J. Pharm. Biopharm. 72, 76–82 (2009)

    CAS  PubMed  Google Scholar 

  79. Agueros, M., Zabaleta, V., Espuelas, S., Campanero, M.A., Irache, J.M.: Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly (anhydride) nanoparticles. J. Control. Release 145, 2–8 (2010)

    CAS  PubMed  Google Scholar 

  80. Pathak, S.M., Musmade, P., Dengle, S., Karthik, A., Bhat, K., Udupa, N.: Enhanced oral absorption of saquinavir with methyl-beta-cyclodextrin—preparation and in vitro and in vivo evaluation. Eur. J. Pharm. Sci. 41, 440–451 (2010)

    CAS  PubMed  Google Scholar 

  81. Liu, M., Cao, W., Sun, Y., He, Z.: Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin. Int. J. Pharm. 477, 159–166 (2014)

    CAS  PubMed  Google Scholar 

  82. Lin, C., Chen, F., Ye, T., Zhang, L., Zhang, W., Liu, D., Pan, W.: A novel oral delivery system consisting in “drug-in cyclodextrin-in nanostructured lipid carriers” for poorly water-soluble drug: vinpocetine. Int. J. Pharm. 465, 90–96 (2014)

    CAS  PubMed  Google Scholar 

  83. Chattah, A.K., Pfund, L.Y., Zoppi, A., Longhi, M.R., Garnero, C.: Toward novel antiparasitic formulations: complexes of albendazole desmotropes and β-cyclodextrin. Carbohydr. Polym. 164, 379–385 (2017)

    CAS  PubMed  Google Scholar 

  84. Celebioglu, A., Uyar, T.: Fast dissolving oral drug delivery system based on electrospun nanofibrous webs of cyclodextrin/ibuprofen inclusion complex nanofibers. Mol. Pharm. 16, 4387–4398 (2019)

    CAS  PubMed  Google Scholar 

  85. Celebioglu, A., Uyar, T.: Metronidazole/Hydroxypropyl-β-Cyclodextrin inclusion complex nanofibrous webs as fast-dissolving oral drug delivery system. Int. J. Pharm. 572, 118828 (2019)

    CAS  PubMed  Google Scholar 

  86. Celebioglu, A., Uyar, T.: Development of ferulic acid/cyclodextrin inclusion complex nanofibers for fast-dissolving drug delivery system. Int. J. Pharm. 584, 119395 (2020)

    CAS  PubMed  Google Scholar 

  87. Turker, S., Onur, E., Ozer, Y.: Nasal route and drug delivery systems. Pharm. World Sci. 26, 137–142 (2004)

    PubMed  Google Scholar 

  88. Marttin, E., Verhoef, J.C., Merkus, F.W.H.M.: Efficacy, safety and mechanism of cyclodextrins as absorption enhancers in nasal delivery of peptide and protein drugs. J. Drug Target. 6, 17–36 (1998)

    CAS  PubMed  Google Scholar 

  89. Merkus, F.W.H.M., Verhoef, J.C., Marttin, E., Romeijn, S.G., Van der Kuy, P.H.M., Hermens, W.A.J.J., Schipper, N.G.M.: Cyclodextrins in nasal drug delivery. Adv. Drug Deliv. Rev. 36, 41–57 (1999)

    CAS  PubMed  Google Scholar 

  90. Adjei, A., Sundberg, D., Miller, J., Chun, A.: Bioavailability of leuprolide acetate following nasal and inhalation delivery to rats and healthy humans. Pharm. Res. 9, 244–249 (1992)

    CAS  PubMed  Google Scholar 

  91. Merkus, F.W., Schipper, N.G., Verhoef, J.C.: The influence of absorption enhancers on intranasal insulin absorption in normal and diabetic subjects. J. Controlled Release 41, 69–75 (1996)

    CAS  Google Scholar 

  92. Kondo, T., Nishimura, K., Irie, T., Uekama, K.: Cyclodextrin derivatives that modify nasal absorption of morphine and its entry into cerebrospinal fluid in the rat. Pharm. Pharmacol. Commun. 1, 163–166 (1995)

    CAS  Google Scholar 

  93. Irie, T., Uekama, K.: Pharmaceutical applications of cyclodextrins. III. Toxicological issues and safety evaluation. J. Pharm. Sci. 86, 147–162 (1997)

    CAS  PubMed  Google Scholar 

  94. Schwarz, D.H., Engelke, A., Wenz, G.: Solubilizing steroidal drugs by β-cyclodextrin derivatives. Int. J. Pharm. 531, 559–567 (2017)

    CAS  PubMed  Google Scholar 

  95. Le Bourlais, C., Acar, L., Zia, H., Sado, P.A., Needham, T., Leverge, R.: Ophthalmic drug delivery systems-recent advances. Progr. Retinal Eye Res. 17, 33–58 (1998)

    CAS  Google Scholar 

  96. Loftsson, T., Stefansson, E.: Effect of cyclodextrins on topical drug delivery to the eye. Drug Dev. Ind. Pharm. 23, 473–481 (1996)

    Google Scholar 

  97. Loftssona, T., Jarvinen, T.: Cyclodextrins in ophthalmic drug delivery. Adv. Drug Deliv. Rev. 36, 59–79 (1999)

    CAS  PubMed  Google Scholar 

  98. Jarvinen, K., Jarvinen, T., Thompson, D.O., Stella, V.J.: The effect of a modified β-cyclodextrin, SBE4-β-CD, on the aqueous stability and ocular absorption of pilocarpine. Curr. Eye Res. 13, 897–905 (1994)

    CAS  PubMed  Google Scholar 

  99. Jarvinen, K., Jarvinen, T., Urtti, A.: Ocular absorption following topical delivery. Adv. Drug Deliv. Rev. 16, 3–19 (1995)

    Google Scholar 

  100. Kristinsson, J.K., Fridriksdottir, H., Thorisdottir, S., Sigurdardottir, A.M., Stefansson, E., Loftsson, T.: Dexamethasone-cyclodextrin-polymer co-complexes in aqueous eye drops. Aqueous humor pharmacokinetics in humans. Investig. Ophthalmol. Vis. Sci. 37, 1199–1203 (1996)

    CAS  Google Scholar 

  101. Jarho, P., Urtti, A., Jarvinen, K., Pate, D.W., Jarvinen, T.: Hydroxypropyl-β-cyclodextrin increases aqueous solubility and stability of anandamide. Life Sci. 58, 181–185 (1996)

    Google Scholar 

  102. Utsuki, T., Imamura, K., Hirayama, F., Uekama, K.: Stoichiometry-dependent changes of solubility and photoreactivity of an antiulcer agent, 2′-carboxymethoxy-4, 4′-bis (3-methyl-2-butenyloxy) chalcone, in cyclodextrin inclusion complexes. Eur. J. Pharm. Sci. 1, 81–87 (1993)

    CAS  Google Scholar 

  103. Fridriksdottir, H., Loftsson, T., Stefansson, E.: Formulation and testing of methazolamide cyclodextrin eye drop solutions. J. Control. Release 44, 95–99 (1997)

    CAS  Google Scholar 

  104. Jarho, P., Jarvinen, K., Urtti, A., Stella, V.J., Jarvinen, T.: Modified β-cyclodextrin (sbe7-β-cyd) with viscous vehicle improves the ocular delivery and tolerability of pilocarpine prodrug in rabbits. J. Pharm. Pharmacol. 48, 263–269 (1996)

    CAS  PubMed  Google Scholar 

  105. Matsuda, H., Arima, H.: Cyclodextrins in transdermal and rectal delivery. Adv. Drug Deliv. Rev. 36, 81–99 (1999)

    CAS  PubMed  Google Scholar 

  106. Sigurdoardottir, A.M., Loftsson, T.: The effect of polyvinyl pyrrolidone on cyclodextrin complexation of hydrocortisone and its diffusion through hairless mouse skin. Int. J. Pharm. 126, 73–78 (1995)

    Google Scholar 

  107. Glomot, F., Benkerrour, L., Duchene, D., Poelman, M.C.: Improvement in availability and stability of a dermocorticoid by inclusion in β-cyclodextrin. Int. J. Pharm. 46, 49–55 (1988)

    CAS  Google Scholar 

  108. Tomono, K., Gotoh, H., Okamura, M., Horioka, M., Ueda, H., Nagai, T.: Effect of β-cyclodextrins on sustained release of nitroglycerin from ointment bases. InChem. Abstr. 115, 22–28 (1991)

    Google Scholar 

  109. Tiwari, G., Tiwari, R., Rai, A.K.: Cyclodextrins in delivery systems: applications. J. Pharm Bioall. Sci. 2, 72 (2010)

    CAS  Google Scholar 

  110. Hoshino, T., Ishida, K., Irie, T., Uekama, K., Ono, T.: An attempt to reduce the photosensitizing potential of chlorpromazine with the simultaneous use of β-and dimethyl-β-cyclodextrins in guinea pigs. Arch. Dermatol. Res. 281, 60–65 (1989)

    CAS  PubMed  Google Scholar 

  111. Uekama, K., Arimori, K., Sakai, A., Masaki, K., Irie, T., Otagiri, M.: Improvement in percutaneous absorption of prednisolone by β-and γ-cyclodextrin complexations. Chem. Pharm. Bull. 35, 2910–2913 (1987)

    CAS  Google Scholar 

  112. Uekama, K., Masaki, K., Arimori, K., Irie, T., Hirayama, F.: Effects of beta-and dimethyl beta-cyclodextrins on release and percutaneous absorption behaviors of prednisolone from some ointment bases. Yakugaku Zasshi 107, 449 (1987)

    CAS  PubMed  Google Scholar 

  113. Orienti, I., Zecchi, V., Bertasi, V., Fini, A.: Release of ketoprofen from dermal bases in presence of cyclodextrins: effect of the affinity constant determined in semisolid vehicles. Arch. Pharm. 324, 943–947 (1991)

    CAS  Google Scholar 

  114. Vollmer, U., Muller, B.W., Peeters, J., Mesens, J., Wilffert, B., Peters, T.: A study of the percutaneous absorption-enhancing effects of cyclodextrin derivatives in rats. J. Pharm. Pharmacol. 46, 19–22 (1994)

    CAS  PubMed  Google Scholar 

  115. Bentley, M.V.L., Vianna, R.F., Wilson, S., Collett, J.H.: Characterization of the influence of some cyclodextrins on the stratum corneum from the hairless mouse. J. Pharm. Pharmacol. 49, 397–402 (1997)

    CAS  PubMed  Google Scholar 

  116. Legendre, J.Y., Rault, I., Petit, A., Luijten, W., Demuynck, I., Horvath, S., Cuine, A.: Effects of β-cyclodextrins on skin: implications for the transdermal delivery of piribedil and a novel cognition enhancing-drug, S-9977. Eur. J. Pharm. Sci. 3, 311–322 (1995)

    CAS  Google Scholar 

  117. Kawahara, K., Ueda, H., Tomono, K., Nagai, T.S.T.P.: Effect of diethyl β-cyclodextrin on the release and absorption behaviour of indomethacin from ointment bases. STP Pharma Sci. 2, 506–513 (1992)

    CAS  Google Scholar 

  118. McCormack, B., Gregoriadis, G.: Drugs-in-cyclodextrins-in liposomes: a novel concept in drug delivery. Int. J. Pharm. 112, 249–258 (1994)

    CAS  Google Scholar 

  119. Maestrelli, F., Gonzalez-Rodriguez, M.L., Rabasco, A.M., Mura, P.: Effect of preparation technique on the properties of liposomes encapsulating ketoprofen–cyclodextrin complexes aimed for transdermal delivery. Int. J. Pharm. 312, 53–60 (2006)

    CAS  PubMed  Google Scholar 

  120. Adachi, H., Irie, T., Harayama, F., Uekame, K.: Stabilization of prostaglandin E1 in fatty alcohol propylene glycol ointment by acidic cyclodextrin derivative, O-carboxymethyl-O-ethyl-β-cyclodextrin. Chem. Pharm. Bull. 40, 1586–1591 (1992)

    CAS  Google Scholar 

  121. Tenjarla, S., Puranajoti, P., Kasina, R., Mandal, T.: Preparation characterization evaluation of miconazole-cyclodextrin complexes for improved oral topical delivery. J. Pharm. Sci. 87, 425–429 (1998)

    CAS  PubMed  Google Scholar 

  122. Lopez, R.F., Collett, J.H., Bentley, M.V.L.: Influence of cyclodextrin complexation on the in vitro permeation and skin metabolism of dexamethasone. Int. J. Pharm. 200, 127–132 (2000)

    CAS  PubMed  Google Scholar 

  123. Lin, S.Z., Wouessidjewe, D., Poelman, M.C., Duchene, D.: In vivo evaluation of indomethacin/cyclodextrin complexes gastrointestinal tolerance and dermal anti-inflammatory activity. Int. J. Pharm. 106, 63–67 (1994)

    CAS  Google Scholar 

  124. Celebi, N., Kislal, O., Tarimci, N.: The effect of β-cyclodextrin and penetration additives on the release of naproxen from ointment bases. Pharmazie. 48, 914–917 (1993)

    CAS  Google Scholar 

  125. Abdel Rahman, A.A., Khidr, S.H., Ahmed, S.M., Aboutaleb, A.E.: Evaluation of chloramphenicol-β-cyclodextrin inclusion complex. Eur. J. Pharm. Biopharm. 37, 34–37 (1991)

    CAS  Google Scholar 

  126. Loftsson, T., Frioriksdottir, H., Ingvarsdottir, G., Jonsdottir, B., Siguroardottir, A.M.: The influence of 2-hydroxypropyl-β-cyclodextrin on diffusion rates and transdermal delivery of hydrocortisone. Drug Dev. Ind. Pharm. 20, 1699–1708 (1994)

    CAS  Google Scholar 

  127. Udupa, N., Bhat, L.: Evaluation of FEW ciprofloxacin (CIP) and norfloxacin (NOR) formulations. Drug Dev. Ind. Pharm. 18, 2197–2205 (1992)

    CAS  Google Scholar 

  128. Szeman, J., Ueda, H., Szejtli, J., Fenyvesi, E., Watanabe, Y., Machida, Y., Nagai, T.: Enhanced percutaneous absorption of homogenized tolnaftate/beta-cyclodextrin polymer ground mixture. Drug Des. Deliv. 1, 325–332 (1987)

    CAS  PubMed  Google Scholar 

  129. Amidouche, D., Montassier, P., Poelman, M.C., Duchene, D.: Evaluation by laser doppler velocimetry of the attenuation of tretinoin induced skin irritation by β-cyclodextrin complexation. Int. J. Pharm. 111, 111–116 (1994)

    Google Scholar 

  130. Loftsson, T., Sigurdardottir, A.M.: The effect of polyvinylpyrrolidone and hydroxypropyl methylcellulose on HPβCD complexation of hydrocortisone and its permeability through hairless mouse skin. Eur. J. Pharm. Sci. 2, 297–301 (1994)

    CAS  Google Scholar 

  131. Iervolino, M., Cappello, B., Raghavan, S.L., Hadgraft, J.: Penetration enhancement of ibuprofen from supersaturated solutions through human skin. Int. J. Pharm. 212, 131–141 (2001)

    CAS  PubMed  Google Scholar 

  132. Lee, B.J., Cui, J.H., Parrott, K.A., Ayres, J.W., Sack, R.L.: Percutaneous absorption and model membrane variations of melatonin in aqueous-based propylene glycol and 2-hydroxypropyl-β-cyclodextrin vehicles. Arch. Pharmacal Res. 21, 503–507 (1998)

    CAS  Google Scholar 

  133. Doliwa, A., Santoyo, S., Ygartua, P.: Transdermal iontophoresis and skin retention of piroxicam from gels containing piroxicam: hydroxypropyl-β-cyclodextrin complexes. Drug Dev. Ind. Pharm. 27, 751–758 (2001)

    CAS  PubMed  Google Scholar 

  134. Thorsteinn Loftsson, B.J.O., Bodora, N.: The effects of cyclodextrins on transdermal delivery of drugs. Eur. J. Pharm. Biopharm. 37, 1 (1991)

    Google Scholar 

  135. Moraes, C.M., Abrami, P., De Araujo, D.R., Braga, A.F., Issa, M.G., Ferraz, H.G., Fraceto, L.F.: Characterization of lidocaine: hydroxypropyl-β-cyclodextrin inclusion complex. J. Incl. Phenom. Macrocycl. Chem. 57, 313–316 (2007)

    CAS  Google Scholar 

  136. Okamoto, H., Komatsu, H., Hashida, M., Sezaki, H.: Effects of β-cyclodextrin and di-O-methyl-β-cyclodextrin on the percutaneous absorption of butylparaben, indomethacin and sulfanilic acid. Int. J. Pharm. 30, 35–45 (1986)

    CAS  Google Scholar 

  137. Chang, S.L., Banga, A.K.: Transdermal iontophoretic delivery of hydrocortisone from cyclodextrin solutions. J. Pharm. Pharmacol. 50, 635–640 (1998)

    CAS  PubMed  Google Scholar 

  138. Nonaka, N., Farr, S.A., Kageyama, H., Shioda, S., Banks, W.A.: Delivery of galanin-like peptide to the brain: targeting with intranasal delivery and cyclodextrins. J. Pharmacol. Exp. Ther. 325, 513–519 (2008)

    CAS  PubMed  Google Scholar 

  139. Uekama, K., Otagiri, M., Sakai, A., Irie, T., Matsuo, N., Matsuoka, Y.: Improvement in the percutaneous absorption of beclomethasone dipropionate by γ-cyclodextrin complexation. J. Pharm. Pharmacol. 37, 532–535 (1985)

    CAS  PubMed  Google Scholar 

  140. Lengyel, M.T., Szejtli, J.: Menadione-γ-cyclodextrin inclusion complex. J. Incl. Phenom. 3, 1–8 (1985)

    CAS  Google Scholar 

  141. Argenziano, M., Haimhoffer, A., Bastiancich, C., Jicsinszky, L., Caldera, F., Trotta, F., Castagnoli, C.: In vitro enhanced skin permeation and retention of imiquimod loaded in β-cyclodextrin nanosponge hydrogel. Pharmaceutics. 11, 138 (2019)

    CAS  PubMed Central  Google Scholar 

  142. Kim, J.K., Kim, M.S., Park, J.S., Kim, C.K.: Thermo-reversible flurbiprofen liquid suppository with HP-β-CD as a solubility enhancer: improvement of rectal bioavailability. J. Incl. Phenom. Macrocycl. Chem. 64, 265–272 (2009)

    CAS  Google Scholar 

  143. Kondo, T., Irie, T., Uekama, K.: Combination effects of α-cyclodextrin and xanthan gum on rectal absorption and metabolism of morphine from hollow-type suppositories in rabbits. Biol. Pharm. Bull. 19, 280–286 (1996)

    CAS  PubMed  Google Scholar 

  144. Masahiko, K., Fumitoshi, H., Kaneto, U.: Improvement of oral and rectal bioavailabilities of carmofur by methylated β-cyclodextrin complexations. Int. J. Pharm. 38, 191–198 (1987)

    Google Scholar 

  145. Uekama, K., Imai, T., Maeda, T., Irie, T., Hirayama, F., Otagiri, M.: Improvement of dissolution and suppository release characteristics of flurbiprofen by inclusion complexation with heptakis (2, 6-di-O-methyl)-β-cyclodextrin. J. Pharm. Sci. 74, 841–845 (1985)

    CAS  PubMed  Google Scholar 

  146. Arima, H., Kondo, T., Irie, T., Hirayama, F., Uekama, K., Miyaji, T., Inoue, Y.: Use of water-soluble beta-cyclodextrin derivatives as carriers of anti-inflammatory drug biphenylylacetic acid in rectal delivery. Yakugaku Zasshi 112, 65–72 (1992)

    CAS  PubMed  Google Scholar 

  147. Arima, H., Kondo, T., Irie, T., Uekama, K.: Enhanced rectal absorption and reduced local irritation of the anti-inflammatory drug ethyl 4-biphenylylacetate in rats by complexation with water-soluble β-cyclodextrin derivatives and formulation as oleaginous suppository. J. Pharm. Sci. 81, 1119–1125 (1992)

    CAS  PubMed  Google Scholar 

  148. Arima, H., Irie, T., Uekama, K.: Differences in the enhancing effects of water soluble β-cyclodextrins on the release of ethyl 4-biphenylyl acetate, an anti-inflammatory agent from an oleaginous suppository base. Int. J. Pharm. 57(2), 107–115 (1989)

    CAS  Google Scholar 

  149. Uekama, K., Kondo, T., Nakamura, K., Irie, T., Arakawa, K., Shibuya, M., Tanaka, J.: Modification of rectal absorption of morphine hollow-type suppositories with a combination of α-cyclodextrin and viscosity-enhancing polysaccharide. J. Pharm. Sci. 84, 15–20 (1995)

    CAS  PubMed  Google Scholar 

  150. Pitha, J., Harman, S.M., Michel, M.E.: Hydrophilic cyclodextrin derivatives enable effective oral administration of steroidal hormones. J. Pharm. Sci. 75, 165–167 (1986)

    CAS  PubMed  Google Scholar 

  151. Hoon, T.J., Dawood, M.Y., Khan-Dawood, F.S., Ramos, J., Batenhorst, R.L.: Bioequivalence of a 17β-estradiol hydroxypropyl-β-cyclodextrin complex in postmenopausal women. J. Clin. Pharmacol. 33, 1116–1121 (1993)

    CAS  PubMed  Google Scholar 

  152. Brown, G.A., Martini, E.R., Roberts, B.S., Vukovich, M.D., King, D.S.: Acute hormonal response to sublingual androstenediol intake in young men. J. Appl. Physiol. 92, 142–146 (2002)

    CAS  PubMed  Google Scholar 

  153. Yoo, S.D., Yoon, B.M., Lee, H.S., Lee, K.C.: Increased bioavailability of clomipramine after sublingual administration in rats. J. Pharm. Sci. 88, 1119–1121 (1999)

    CAS  PubMed  Google Scholar 

  154. Badawy, S.I.F., Ghorab, M.M., Adeyeye, C.M.: Bioavailability of danazol-hydroxypropyl-β-cylodextrin complex by different routes of administration. Int. J. Pharm. 145, 137–143 (1996)

    CAS  Google Scholar 

  155. Bilensoy, E., Hincal, A.A.: Recent advances and future directions in amphiphilic cyclodextrin nanoparticles. Exp. Opin. Drug Deliv. 6, 1161–1173 (2009)

    CAS  Google Scholar 

  156. Mori, T., Tsuchiya, R., Doi, M., Nagatani, N., Tanaka, T.: Solubilization of ultraviolet absorbers by cyclodextrin and their potential application in cosmetics. J. Incl. Phenom. Macrocycl. Chem. 93, 91–96 (2019)

    CAS  Google Scholar 

  157. Kfoury, M., Hadaruga, N. G., Hadaruga, D. I., Fourmentin, S.: Cyclodextrins as encapsulation material for flavors and aroma. In: Nanotechnology in the Agri-Food Industry, Academic Press (2016)

  158. Ryzhakov, A., Do Thi, T., Stappaerts, J., Bertoletti, L., Kimpe, K., Couto, A.R.S., Kurkov, S.: Self-assembly of cyclodextrins and their complexes in aqueous solutions. J. Pharm. Sci. 105, 2556–2569 (2016)

    CAS  PubMed  Google Scholar 

  159. Cova, T. F. G. G., Cruz, S. M., Valente, A. J., Abreu, P. E., Marques, J. M., & Pais, A. A.: Aggregation of cyclodextrins: fundamental issues and applications. Springer Nature Switzerland AG Basel. In Cyclodextrin Fundamentals, Reactivity and Analysis, pp. 45-65 (2018)

  160. Jansook, P., Ogawa, N., Loftsson, T.: Cyclodextrins: structure, physicochemical properties and pharmaceutical applications. Int. J. Pharm. 535, 272–284 (2018)

    CAS  PubMed  Google Scholar 

  161. Conceiçao, J., Farto-Vaamonde, X., Goyanes, A., Adeoye, O., Concheiro, A., Cabral-Marques, H., Alvarez-Lorenzo, C.: Hydroxypropyl-β-cyclodextrin-based fast dissolving carbamazepine printlets prepared by semisolid extrusion 3D printing. Carbohydr. Polym. 221, 55–62 (2019)

    PubMed  Google Scholar 

  162. Gerloczy, A., Fonagy, A., Keresztes, P., Perlaky, L., Szejtli, J.: Absorption, distribution, excretion and metabolism of orally administered 14C-beta-cyclodextrin in rat. Arzneimittelforschung 35, 1042–1047 (1985)

    CAS  PubMed  Google Scholar 

  163. Duchene, D., Bachot, A., Loftsson, T.: Les cyclodextrines et leurs utilisations en pharmacie et cosmetologie. STP Pharma Pratiques. 19, 15–27 (2009)

    CAS  Google Scholar 

  164. Frank, D.W., Gray, J.E., Weaver, R.N.: Cyclodextrin nephrosis in the rat. Am. J. Pathol. 83, 367 (1976)

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Perrin, J.H., Field, F.P., Hansen, D.A., Mufson, R.A., Torosian, G.: Beta-Cyclodextrin as an aid to peritoneal dialysis. Renal toxicity of beta-cyclodextrin in the rat. Res. Commun. Chem. Pathol. Pharmacol. 19, 373–376 (1978)

    CAS  PubMed  Google Scholar 

  166. Gould, S., Scott, R.C.: 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD): a toxicology review. Food Chem. Toxicol. 43, 1451–1459 (2005)

    CAS  PubMed  Google Scholar 

  167. Van De Manakker, F., Vermonden, T., Van Nostrum, C.F., Hennink, W.E.: Cyclodextrin-based polymeric materials: synthesis, properties, and pharmaceutical/biomedical applications. Biomacromol 10, 3157–3175 (2009)

    Google Scholar 

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    Priya Dhiman & Meenakshi Bhatia

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Dhiman, P., Bhatia, M. Pharmaceutical applications of cyclodextrins and their derivatives. J Incl Phenom Macrocycl Chem 98, 171–186 (2020). https://doi.org/10.1007/s10847-020-01029-3

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