Comparative study of β-cyclodextrin derivatives with amlodipine inclusion complexes for enhanced solubility, drug...

Amlodipine (AMD), a calcium channel blocker, has become a viable anticancer treatment because of its biological properties. However, its poor water solubility and low bioavailability hinder its physiological activities and therapeutic applications when administered orally. In this study, inclusion complexes (ICs) of AMD with pure cyclodextrins (CDs) and three different CD derivatives, namely hydroxypropyl β-cyclodextrin (HD), methyl-β-cyclodextrin (MD), and sulfobutylether-β-cyclodextrin (SD), were prepared, and their physicochemical and biological properties were compared. The enhanced solubility of AMD:CD IC formation in aqueous media was measured using UV-Vis and fluorescence spectroscopy, and the binding constants were calculated using the Benesi-Hildebrand method. In addition, phase solubility studies confirmed the formation of 1:1 ICs, which followed an A_L-type profile. Among the various CD derivatives, AMD:SD exhibited a high apparent stability constant (K_1:1) of 1447.5 M^-1, indicating a strong affinity between SD and AMD. The AMD:CDs (1:1) ICs were prepared using the co-precipitation method and characterized to identify the functional groups, crystallinity, morphological changes, and thermal stability, which indicated the successful encapsulation of AMD within CDs. Moreover, molecular docking studies confirmed the encapsulation of AMD within CDs with favorable binding energy and stable interactions. Drug release studies showed an initial burst release followed by a sustained release after 20 min, and the release percentage for the AMD:CDs was between 82 and 98 %. Finally, the AMD:CDs ICs exhibited superior cell viability and cellular uptake in HCT-116 cells using the WST-1 assay compared to that of pure AMD and CDs.