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    pH-responsive magnetic cyclodextrin-liposome nanoplatforms for stabilization and targeted delivery of topotecan
    (Elsevier, 2026) Tural, Bilsen; Ertas, Erdal; Kurucay, Ali; Ates, Burhan; Tural, Servet
    Topotecan (TPT), a potent anticancer agent, suffers from rapid hydrolysis of its active lactone ring under physiological conditions, severely limiting its clinical efficacy. To address this challenge, we developed a novel pH-responsive, magnetic drug delivery system integrating (3-cyclodextrin-functionalized Fe3O4 nanoparticles (Fe3O4@(3-CD) and liposomes. Fe3O4@(3-CD nanoparticles were synthesized via chemical co-precipitation and then loaded with TPT via host-guest complexation. The resulting Fe3O4@(3-CD@TPT complexes were encapsulated into liposomes using the sonication method to increase drug stability, maintain the stable lactone form, and achieve controlled release. Characterization by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Fourier Transform Infrared Spectroscopy (FTIR), High-Performance Liquid Chromatography (HPLC), and Vibrating Sample Magnetometry (VSM) confirmed the successful formulation. In vitro drug release studies demonstrated a diffusion-controlled release profile, while the pH responsiveness of the system was primarily governed by pH-dependent drug stabilization and loading efficiency rather than pronounced differences in release kinetics. Cytotoxicity assays against MCF-7 breast cancer cells showed that the Fe3O4@(3CD@TPT@Liposome formulation exhibited significantly lower IC50 values compared to free TPT and Fe3O4@(3CD@TPT complexes. These results highlight the potential of the magnetic cyclodextrin-liposome hybrid platform as an effective strategy for the targeted and controlled delivery of pH-sensitive chemotherapeutics such as topotecan.