Exploring the Inclusion Complex of an Anticancer Drug with β-Cyclodextrin for Reducing Cytotoxicity Toward the Normal Human Cell Line by an Experimental and Computational Approach

[Image: see text] The toxicity of any drug against normal cells is a health hazard for all humans. At present, health and disease researchers from all over the world are trying to synthesize designer drugs with diminished toxicity and side effects. The purpose of the present study is to enhance the bioavailability and biocompatibility of gemcitabine (GEM) by decreasing its toxicity and reducing deamination during drug delivery by incorporating it inside the hydrophobic cavity of β-cyclodextrin (β-CD) without affecting the drug ability of the parent compound (GEM). The newly synthesized inclusion complex (IC) was characterized by different physical and spectroscopic techniques, thereby confirming the successful incorporation of the GEM molecule into the nanocage of β-CD. The molecular docking study revealed the orientation of the GEM molecule into the β-CD cavity (−5.40 kcal/mol) to be stably posed for ligand binding. Photostability studies confirmed that the inclusion of GEM using β-CD could lead to better stabilization of GEM (≥96%) for further optical and clinical applications. IC (GEM-β-CD) and GEM exhibited effective antibacterial and antiproliferative activities without being metabolized in a dose-dependent manner. The CT-DNA analysis showed sufficiently strong IC (GEM-β-CD) binding (K(a) = 8.1575 × 10(10)), and this interaction suggests that IC (GEM-β-CD) may possibly exert its biological effects by targeting nucleic acids in the host cell. The newly synthesized biologically active IC (GEM-β-CD), a derivative of GEM, has pharmaceutical development potentiality.