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

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.