Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Formation & specification of host–guest inclusion complexes of an anti-malarial drug inside into cyclic oligosaccharides for enhancing bioavailability

  • 16 Accesses


The purpose of this novel research is to explore the formation of inclusion complexes of a drug, namely, chloroquine diphosphate with cyclic oligosaccharides. The solubility, versatility and bioavailability of the drug are enhanced and some of its side effects are reduced after encapsulation. Various sophisticated approaches have been employed to synthesize and characterize the inclusion phenomenon, which confirm the 1:1 stoichiometry of the complexes. The association constant is found higher in case of β-cyclodextrin which was explicated based on their molecular structure. The work explores the enhancement of overall bioavailability of this essential biologically active molecule.

This is a preview of subscription content, log in to check access.

Scheme 1
Scheme 2
Scheme 3
Fig. 1
Fig. 2
Scheme 4
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8


  1. 1.

    Li, H., Chen, D., Sun, Y., Zheng, Y., Tan, L., Weiss, P.: Viologen-mediated assembly of and sensing with carboxylatopillar[5]arene-modified gold nanoparticles. J. Am. Chem. Soc. 135, 1570–1576 (2013)

  2. 2.

    Negi, J.S., Singh, S.: Spectroscopic investigation on the inclusion complex formation between amisulpride and γ-cyclodextrin. Carbohydr. Polym. 92, 1835–1843 (2013)

  3. 3.

    Roy, M.N., Roy, A., Saha, S.: Probing inclusion complexes of cyclodextrins with amino acids by physicochemical approach. Carbohydr. Polym. 151, 458–466 (2016)

  4. 4.

    Saha, S., Roy, A., Roy, K., Roy, M.N.: Study to explore the mechanism to form inclusion complexes of β-cyclodextrin with vitamin molecules. Sci. Rep. 6, 35764 (2016)

  5. 5.

    Roy, A., Saha, S., Dutta, B., Roy, M.N.: Insertion behavior of imidazolium and pyrrolidinium based ionic liquids into α and β cyclodextrins: mechanism and factors leading to host–guest inclusion complexes. RSC Adv. 6, 100016–100027 (2016)

  6. 6.

    Roy, M.N., Roy, K., Das, K., Barman, B.K.: Self assembly inclusion of green solvents with oligosachharides. J. Mol. Liq. 216, 432–436 (2016)

  7. 7.

    Dutta, B., Barman, S., Roy, M.N.: Self assembly inclusion of ionic liquid into holo cylinder oligosaccharides. J. Mol. Liq. 214, 264–269 (2016)

  8. 8.

    Wei, B.: β-Cyclodextrin associated polymeric systems: rheology, flow behavior in porous media and enhanced heavy oil recovery performance. Carbohydr. Polym. 134, 398–405 (2015)

  9. 9.

    Pinho, E., Grootveld, M., Soares, G., Henriques, M.: Cyclodextrins as encapsulation agents for plant bioactive compounds. Carbohydr. Polym. 101, 121–135 (2014)

  10. 10.

    Aytac, Z., Yildiz, Z.I., Kayaci-Senirmak, F., Keskin, N.O.S., Kusku, S.I., Durgun, T.E., Uyar, T.: Fast-dissolving, prolonged release, and antibacterial cyclodextrin/limonene-inclusion complex nanofibrous webs via polymer-free electrospinning. J. Agric. Food Chem. 64, 7325–7334 (2016)

  11. 11.

    Yao, Y., Liu, X., Liu, T., Zhou, J., Zhu, J., Sun, G., He, D.: Preparation of inclusion complex of perfluorocarbon compound with β-cyclodextrin for ultrasound contrast agent. RSC Adv. 5, 6305 (2015)

  12. 12.

    Dinar, K., Sahra, K., Seridi, A., Kadri, M.: Inclusion complexes of N-sulfamoyloxazolidinones with β-cyclodextrin: a molecular modeling approach. Chem. Phys. Lett. 595–596, 113–120 (2014)

  13. 13.

    "Aralen Phosphate". The American Society of Health-System Pharmacists. Accessed 2 Dec 2015

  14. 14.

    Health information for international travel 2001. U.S. Department of Health and Human Services, Public Health Service, Atlanta (2001)

  15. 15.

    DailyMed—CHLOROQUINE- chloroquine phosphate tablet CHLOROQUINE- chloroquine phosphate tablet, coated. Accessed 3 Nov 2015

  16. 16.

    Bani-Yaseen, A.D., Mo’ala, A.: Spectral, thermal, and molecular modeling studies on the encapsulation of selected sulfonamide drugs in β-cyclodextrin nano-cavity. Spectrochim. Acta A 131, 424–431 (2014)

  17. 17.

    Wang, L., Li, S., Tang, P., Yan, J., Xu, K., Li, H.: Characterization and evaluation of synthetic riluzole with β-cyclodextrin and 2,6-di-O-methyl-β-cyclodextrin inclusion complexes. Carbohydr. Polym. 129, 9–16 (2015)

  18. 18.

    Saha, S., Ray, T., Basak, S., Roy, M.N.: NMR, surface tension and conductivity studies to determine inclusion mechanism: thermodynamics of host–guest inclusion complexes of natural amino acids in aqueous cyclodextrins. New J. Chem. 40, 651–661 (2016)

  19. 19.

    Caso, J.V., Russo, L., Palmieri, M., Malgieri, G., Galdiero, S., Falanga, A., Isernia, C., Iacovino, R.: Investigating the inclusion properties of aromatic amino acids complexing beta-cyclodextrins in model peptides. Amino Acids 47, 2215–2227 (2015)

  20. 20.

    Wang, T., Wang, M.D., Ding, C., Fu, J.: Mono-benzimidazole functionalized β-cyclodextrins as supramolecular nanovalves for pH-triggered release of p-coumaric acid. Chem. Commun. 50, 12469–12472 (2014)

  21. 21.

    Roy, M.N., Saha, S., Barman, S., Ekka, D.: Host–guest inclusion complexes of RNA nucleosides insight into aqueous cyclodextrins explored by physicochemical and spectroscopic contrivances. RSC Adv. 6, 8881–8891 (2016)

  22. 22.

    Gao, Y., Zhao, X., Dong, B., Zheng, L., Li, N., Zhang, S.: Inclusion complexes of β-cyclodextrin with ionic liquid surfactants. J. Phys. Chem. B 110, 8576–8581 (2006)

  23. 23.

    Roy, M.N., Ekka, D., Saha, S., Roy, M.C.: Host–guest inclusion complexes of α and β-cylodextrins with α-amino acids. RSC Adv. 4, 42383–42390 (2014)

  24. 24.

    Pineiro, A., Banquy, X., Casas, S.P., Tovar, E., Garcia, A., Villa, A., Amigo, A., Mark, A.E., Costas, M.: On the characterization of host−guest complexes: surface tension, calorimetry, and molecular dynamics of cyclodextrins with a non-ionic surfactant. J. Phys. Chem. B 111, 4383–4392 (2007)

  25. 25.

    Gao, Y., Li, Z., Du, J., Han, B., Li, J., Hou, W., Shen, D., Zheng, L., Zhang, G.: Preparation and characterization of inclusion complexes of β-cyclodextrin with ionic liquid. Chem. Eur. J. 11, 5875–5880 (2005)

  26. 26.

    Apelblat, A., Manzurola, E., Orekhova, Z.: Electrical conductance studies in aqueous solutions with glutamic ions. J. Solut. Chem. 36, 891–900 (2007)

  27. 27.

    Qian, T., Yu, C., Wu, S., Shen, J.: Gold nanoparticles coated polystyrene/reduced graphite oxide microspheres with improved dispersibility and electrical conductivity for dopamine detection. Colloids Surf. B. 112, 310–314 (2013)

  28. 28.

    Roy, A., Saha, S., Roy, M.N.: Study to explore host–guest inclusion complexes of cyclodextrins with biologically active molecules in aqueous environment. Fluid Phase Equilib. 425, 252–258 (2016)

  29. 29.

    Job, P.: Formation and stability of inorganic complexes in solution. Ann. Chim. 9, 113–203 (1928)

  30. 30.

    Renny, J.S., Tomasevich, L., Tallmadge, E.H., Collum, D.B.: Method of continuous variations: applications of job plots to the study of molecular associations in organometallic chemistry. Angew. Chem. Int. Ed. 52, 11998–12013 (2013)

  31. 31.

    Roy, M.N., Saha, S., Kundu, M., Saha, B.C., Barman, S.: Exploration of inclusion complexes of neurotransmitters with β-cyclodextrin by physicochemical techniques. Chem. Phys. Lett. 655–656, 43–50 (2016)

  32. 32.

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

  33. 33.

    Benesi, H.A., Hildebrand, J.H.: A spectrophotometric investigation of the interaction of iodine with aromatic hydrocarbons. J. Chem. Soc. 71, 2703–2707 (1949)

  34. 34.

    Dotsikas, Y., Kontopanou, E., Allagiannis, C., Loukas, Y.L.: Interaction of 6-p-toluidinylnaphthalene-2-sulphonate with beta-cyclodextrin. J. Pharm. Biomed. Anal. 23, 997–1003 (2000)

  35. 35.

    He, Y., Shen, X.: Interaction between β­cyclodextrin and ionic liquids in aqueous solutions investigated by a competitive method using a substituted 3H­indole probe. J. Photochem. Photobiol. A 197, 253–259 (2008)

  36. 36.

    Xiao, C., Li, K., Huanga, R., Hea, G., Zhang, J., Zhu, L., Yang, Q., Jiang, K., Jin, Y., Lin, J.: Investigation of inclusion complex of epothilone A with cyclodextrins. Carbohydr. Polym. 102, 297–305 (2014)

  37. 37.

    Stalin, T., Srinivasan, K., Sivakumar, K., Radhakrishnan, S.: Preparation and characterizations of solid/aqueous phases inclusion complex of 2,4-dinitroaniline with β-cyclodextrin. Carbohydr. Polym. 107, 72–84 (2014)

  38. 38.

    Sivakumar, K., Ragi, T.R., Prema, D., Stalin, T.: Experimental and theoretical investigation on the structural characterization and orientation preferences of 2-hydroxy-1-naphthoic acid/β-cyclodextrin host–guest inclusion complex. J. Mol. Liq. 218, 538–548 (2016)

  39. 39.

    Misiuk, W., Jozefowicz, M.: Study on a host–guest interaction of hydroxypropyl-β-cyclodextrin with ofloxacin. J. Mol. Liq. 202, 101–106 (2015)

  40. 40.

    Rajendiran, N., Siva, S.: Inclusion complex of sulfadimethoxine with cyclodextrins: preparation and characterization. Carbohydr. Polym. 101, 828–836 (2014)

  41. 41.

    Rajendiran, N., Venkatesh, G., Mohandass, T.: Fabrication of 2D nanosheet through self assembly behavior of sulfamethoxypyridazine inclusion complexes with α and β cyclodextrins. Spectrochim. Acta A 123, 158–166 (2014)

  42. 42.

    Zhang, J., Jiang, K., An, K., Ren, S., Xie, X., Jin, Y., Lin, J.: Novel water-soluble fisetin/cyclodextrins inclusion complexes: preparation, characterization, molecular docking and bioavailability. Carbohydr. Res. 418, 20–28 (2015)

  43. 43.

    Okada, Y., Ueyama, K., Nishikawa, J., Semma, M., Ichikawa, A.: A effect of 6-O-α-maltosyl-β-cyclodextrin and its cholesterol inclusion complex on cellular cholesterol levels and ABCA1 and ABCG1 expression in mouse mastocytoma P-815 cells. Carbohydr. Res. 357, 68–74 (2012)

  44. 44.

    Ceborska, M., Zimnicka, M., Wszelaka-Rylik, M., Troc, A.: Characterization of folic acid/native cyclodextrins host guest complexes in solution. J. Mol. Struct. 1109, 114–118 (2016)

  45. 45.

    Szabó, Z., Tóth, G., Völgyi, G., Komjáti, B., Hancu, G., Szente, L., Sohajda, T., Béni, S., Muntean, D.L., Noszál, B.: Chiral separation of asenapine enantiomers by capillary electrophoresis and characterization of cyclodextrin complexes by NMR spectroscopy, mass spectrometry and molecular modeling. J. Pharm. Biomed. Anal. 117, 398–404 (2016)

Download references


Authors convey their thanks to the SAP, Department of Chemistry, UNB under UGC, New Delhi for financial support and necessary instruments to complete the research work. Prof. Roy was also very thankful to UGC, New Delhi, Government of India, for being honored grant under basic scientific research.

Author information

Correspondence to Mahendra Nath Roy.

Ethics declarations

Conflict of interest

The authors announce 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.

Supplementary file1 (DOCX 64 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Roy, A., Saha, S., Roy, D. et al. Formation & specification of host–guest inclusion complexes of an anti-malarial drug inside into cyclic oligosaccharides for enhancing bioavailability. J Incl Phenom Macrocycl Chem (2020).

Download citation


  • Cyclodextrin
  • Chloroquine diphosphate
  • Inclusion complex
  • Thermodynamics
  • Bioavailability