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Vol. 38 No. 3 (2026): Vol 38 Issue 3, 2026

Copyright (c) 2026 SIVAKAMAVALLI JEYACHANDRAN

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Structural and Functional Optimisation of Lomustine through Hydroxypropyl-β-Cyclodextrin Complexation: In vitro and Computational Insights

https://doi.org/10.14233/ajchem.2026.34781
Shanmugapriya Arumugam
Department of Chemistry, AAA College of Engineering and Technology, Amathur, Sivakasi-626005, India
https://orcid.org/0000-0003-4349-2087
Rupa Devi
Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha University, Chennai-600077, India
Balaji Ganesh
Department of Periodontics, Saveetha Dental College and Hospitals, Saveetha University, Chennai-600077, India
Sivakamavalli Jeyachandran
Lab in Biotechnology and Biosignal Transduction, Department of Orthodontics, Saveetha Dental College and Hospital, Saveetha University, Chennai-600077, India
https://orcid.org/0000-0002-2368-0518

Corresponding Author(s) : Sivakamavalli Jeyachandran

sivakamavalli.sdc@saveetha.com

Asian Journal of Chemistry, Vol. 38 No. 3 (2026): Vol 38 Issue 3, 2026

Abstract

This study reports the hydroxypropyl-β-cyclodextrin (HPβCD) complexation as an effective strategy to enhance the solubility and therapeutic efficacy of lomustine (LMT), a poorly water-soluble anticancer drug. Inclusion complexes were synthesized using physical mixing (PM) and microwave irradiation (MWI) methods and characterised with UV-Vis, FTIR, XRD, DSC and SEM techniques. Molecular docking studies confirmed the complex formation, revealing favourable binding energies of 4.1 and -6.4 kcal mol–1. The LMT-HPBCD complex demonstrated significantly improved dissolution properties compared to pure LMT, with the microwave-irradiated complex showing particularly enhanced performance. In vitro cytotoxicity studies against U87-MG glioblastoma cells revealed superior anticancer activity for the complexed formulations, with cell viability reduced to 22.3-38.6% (vs. 45.7-69.8% for PM and 67.3-91.8% for pure LMT). These findings demonstrate that HPβCD complexation effectively enhances both the physico-chemical properties and biological activity of LMT, offering promising potential for improved glioblastoma treatment.

Keywords

Lomustine Hydroxypropyl-β-cyclodextrin Dissolution Anticancer activity
(1)
Arumugam, S.; Devi, R.; Ganesh, B.; Jeyachandran, S. Structural and Functional Optimisation of Lomustine through Hydroxypropyl-β-Cyclodextrin Complexation: In Vitro and Computational Insights. ajc 2026, 38, 601-609.
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References
  1. D.S. Shewach and R.D. Kuchta, Chem. Rev., 109, 2859 (2009); https://doi.org/10.1021/cr900208x
  2. H.S. Hwang, H. Shin, J. Han and K. Na, J. Pharm. Investig., 48, 143 (2018); https://doi.org/10.1007/s40005-017-0377-x
  3. R. Quan, H. Zhang, Z. Li and X. Li, Medicine, 99, e18591 (2020); https://doi.org/10.1097/MD.0000000000018591
  4. R. Stupp, W.P. Mason, M.J. van den Bent, M. Weller, B. Fisher, M.J.B. Taphoorn, K. Belanger, A.A. Brandes, C. Marosi, T. Gorlia, R.C. Janzer, U. Bogdahn, J. Curschmann, J.G. Cairncross, S.K. Ludwin, A. Allgeier, D. Lacombe, E. Eisenhauer and R.O. Mirimanoff, N. Engl. J. Med., 352, 987 (2005); https://doi.org/10.1056/NEJMoa043330
  5. G. Gallant, R. Salvador and H. Dulude, Bioorg. Med. Chem. Lett., 4, 2353 (1994); https://doi.org/10.1016/0960-894X(94)85039-9
  6. C.T. Gnewuch and G. Sosnovsky, Chem. Rev., 97, 829 (1997); https://doi.org/10.1021/cr941192h
  7. C.R. Bethune, R.J. Geyer, A.M. Spence and R.J.Y. Ho, Cancer Res., 61, 3669 (2001).
  8. B. Bittner and R.J. Mountfield, Curr. Opin. Drug Discov. Devel., 5, 59 (2002).
  9. L.-Y. Lim and M.-L. Go, Eur. J. Pharm. Sci., 10, 17 (2000); https://doi.org/10.1016/S0928-0987(99)00084-6
  10. E. Merisko-Liversidge, G.G. Liversidge and E.R. Cooper, Eur. J. Pharm. Sci., 18, 113 (2003); https://doi.org/10.1016/S0928-0987(02)00251-8
  11. J.K. Spence, S.N. Bhattachar, J.A. Wesley, P.J. Martin and S.R. Babu, Drug Dev. Ind. Pharm., 10, 451 (2005).
  12. O.E. Nicolaescu, I. Belu, A.G. Mocanu, V.C. Manda, G. Rău, A.S. Pîrvu, C. Ionescu, F. Ciulu-Costinescu, M. Popescu and M.V. Ciocîlteu, Pharmaceutics, 17, 288 (2025); https://doi.org/10.3390/pharmaceutics17030288
  13. C. Tsunoda, K. Hasegawa, R. Hiroshige, T. Kasai, H. Yokoyama and S. Goto, Mol. Pharmaceutics, 20, 5032 (2023); https://doi.org/10.1021/acs.molpharmaceut.3c00291
  14. I. Spiridon and N. Anghel, Molecules, 30, 3044 (2025); https://doi.org/10.3390/molecules30143044
  15. C.M. Fernandes, M. Teresa Vieira and F.J. B. Veiga, Eur. J. Pharm. Sci., 15, 79 (2002); https://doi.org/10.1016/S0928-0987(01)00208-1
  16. S.W. Jun, M.S. Kim, J.S. Kim, H.J. Park, S. Lee, J.S. Woo and S.J. Hwang, Eur. J. Pharm. Biopharm., 66, 413 (2007); https://doi.org/10.1016/j.ejpb.2006.11.013
  17. C.A. Ventura, I. Giannone, T. Musumeci, R. Pignatello, L. Ragni, C. Landolfi, C. Milanese, D. Paolino and G. Puglisi, Eur. J. Med. Chem., 41, 233 (2006); https://doi.org/10.1016/j.ejmech.2005.11.002
  18. H. Fisli, N. Bensouilah, N. Dhaoui and M. Abdaoui, J. Incl. Phenom. Macrocycl. Chem., 73, 369 (2012); https://doi.org/10.1007/s10847-011-0073-9
  19. I. Khan, J. Pandit, S. Ahmed, S. Zameer, S.A. Nikita, S. Ahmad, S. Bano, M.D. Ansari, P. Solanki, R.N. Jahan, A. Waheed, M. Aqil and Y. Sultana, J. Drug Deliv. Sci. Technol., 75, 103685 (2022); https://doi.org/10.1016/j.jddst.2022.103685
  20. R.N. Marreto, E.E.C.V. Almeida, P.B. Alves, E.S. Niculau, R.S. Nunes, C.R.S. Matos and A.A.S. Araújo, Thermochim. Acta, 475, 53 (2008); https://doi.org/10.1016/j.tca.2008.06.015
  21. N. Ozdemir and S. Ordu, Drug Dev. Ind. Pharm., 24, 19 (1998); https://doi.org/10.3109/03639049809082348
  22. M. Moneghini, B. Bellich, P. Baxa and F. Princivalle, Int. J. Pharm., 361, 125 (2008); https://doi.org/10.1016/j.ijpharm.2008.05.026
  23. M. Cirri, F. Maestrelli, N. Mennini and P. Mura, J. Pharm. Biomed. Anal., 50, 683 (2009); https://doi.org/10.1016/j.jpba.2008.11.003
  24. T. Higuchi and K.A. Connors, Advances in Analytical Chemistry and Instrumentation, Wiley, New York, vol. 4, pp. 117-212 (1965).
  25. T. Loftsson, M. Masson and M.E. Brewster, J. Pharm. Sci., 93, 1091 (2004); https://doi.org/10.1002/jps.20047
  26. P. Mura, M.T. Faucci and P.L. Parrini, Drug Dev. Ind. Pharm., 27, 119 (2001); https://doi.org/10.1081/DDC-100000478
  27. S. Scalia, S. Villani, A. Scatturin, M.A. Vandelli and F. Forni, J. Pharm. (Cairo), 175, 205 (1998).
  28. A.W. Bauer, W.M. Kirby, J.C. Sherris and M. Turck, Am. J. Clin. Pathol., 45(4_ts), 493 (1966); https://doi.org/10.1093/ajcp/45.4_ts.493
  29. T. Mosmann, J. Immunol. Methods, 65, 55 (1983); https://doi.org/10.1016/0022-1759(83)90303-4
  30. C. Zhang, G. Vasmatzis, J.L. Cornette and C. DeLisi, J. Mol. Biol., 267, 707 (1997); https://doi.org/10.1006/jmbi.1996.0859
  31. P. Ahmadi and J.B. Ghasemi, J. Incl. Phenom. Macrocycl. Chem., 79, 401 (2013); https://doi.org/10.1007/s10847-013-0363-5
  32. T. Brewster and T. Loftsson, Adv. Drug Deliv. Rev., 597, 66617 (2007); https://doi.org/10.1016/j.addr.2007.05.012
  33. Y. Nakai, K. Yamamoto, K. Terada and H. Horibe, J. Incl. Phenom., 2, 523 (1984); https://doi.org/10.1007/BF00662218
  34. R.O. Williams III, V. Mahaguna and M. Sriwongjanya, Eur. J. Pharm. Biopharm., 46, 355 (1998); https://doi.org/10.1016/S0939-6411(98)00033-2
  35. S. Agarwal, D. Jangir, P. Singh and R. Mehrotra, J. Photochem. Photobiol. B: Biology, 130, 281 (2014); https://doi.org/10.1016/j.jphotobiol.2013.11.017
  36. V. Nikolic, S. Ilic-Stojanovic, L. Nikolic, M. Cakic, A. Zdravkovic, A. Kapor and M. Popsavin, Hem. Ind., 68, 107 (2014); https://doi.org/10.2298/HEMIND130306034N
  37. P. Paul, U. Gupta, R. Kumar, S. Munagalasetty, H.P. Padhy, R. Nair, S. Mahajan, I. Maji, M. Aalhate, V. Bhandari, S.K. Guru and P.K. Singh, J. Mol. Liq., 399, 124458 (2024); https://doi.org/10.1016/j.molliq.2024.124458
  38. C. Sonia, N. Chetry, T.G. Devi and T. Karlo, Spectrosc. Lett., 57, 128 (2024); https://doi.org/10.1080/00387010.2024.2330605
  39. A. Ahad, Y.A. Bin Jardan, M.Z. Hassan, M. Raish, A. Ahmad, A.M. Al-Mohizea and F.I. Al-Jenoobi, Drug Deliv., 29, 1512 (2022); https://doi.org/10.1080/10717544.2022.2072540
  40. B. Khatun, P. Baishya, A. Ramteke and T.K. Maji, New J. Chem., 44, 4887 (2022); https://doi.org/10.1039/C9NJ04408F
  41. B. Guo, S. Zhong, N. Li, X. Li, J. Yi and M. Jin, Drug Dev. Ind. Pharm., 39, 1638 (2013); https://doi.org/10.3109/03639045.2012.728231
  42. A.P. Mukne and M.S. Nagarsenker, AAPS PharmSciTech, 5, 142 (2004); https://doi.org/10.1208/pt050119
  43. A.P. Sherje, A. Surve and P. Shende, J. Mater. Sci. Mater. Med., 30, 74 (2019); https://doi.org/10.1007/s10856-019-6268-0
  44. M.M. Maitre, M.R. Longhi and G.G. Granero, Drug Dev. Ind. Pharm., 33, 311 (2007); https://doi.org/10.1080/03639040600901978
  45. T. Yamakawa and S. Nishimura, J. Control. Release, 86, 101 (2003); https://doi.org/10.1016/S0168-3659(02)00367-X
  46. S. Uppal, K. Kaur, R. Kumar, N.K. Kahlon, R. Singh and S.K. Mehta, Ultrason. Sonochem., 39, 25 (2017); https://doi.org/10.1016/j.ultsonch.2017.04.007
  47. Y. Bai, C. Liu, F. Xie, R. Ma, L. Zhuo, N. Li and W. Tian, Carbohydr. Polym., 213, 411 (2019); https://doi.org/10.1016/j.carbpol.2019.03.017
  48. Z. Wang and Y. Li, Pharmaceutics, 10, 76 (2018); https://doi.org/10.3390/pharmaceutics10030076
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