Targeted delivery of doxorubicin via cholesteryl-modified cyclodextrin: Antitumor activity in breast, ovarian, and cervical cancer cell lines.

High cytotoxicity towards physiological cells and the development of drug resistance remain major challenges in anticancer therapy. The use of drug delivery systems for doxorubicin hydrochloride (DOX·HCl) aims to enhance its selective accumulation in cancer cells and reduce adverse effects on normal tissues. In this study, complexation efficiency was assessed through spectroscopic analysis and computational chemistry methods, while cytotoxicity was evaluated using in vitro assays on selected cell lines, including normal cells (CCd1079Sk) and cancerous cells (MCF-7, HeLa, and SKOV-3). The formation and stoichiometry of the inclusion complexes were investigated using UV-Vis and fluorescence spectroscopy, and the experimental data were supported by computational studies confirming the formation of 1:1 complexes. Density functional theory (DFT) calculations performed in both vacuum and DMSO environments revealed the presence of hydrogen bonding interactions that further stabilize the complexes. Importantly, the use of cholesteryl-modified cyclodextrin (CD21chol) enhanced the antiproliferative effect of DOX·HCl on cancer cells and improved the drug's selectivity toward neoplastic cells over normal cells. Overall, the CD21chol:DOX·HCl complexes exhibit favorable physicochemical and biological properties, indicating their promise as a targeted drug delivery system capable of reducing side effects and improving therapeutic outcomes in cancer treatment.