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  • Preparation of complexes based on Laponite® , polydopamine, and polyethyleneimine for doxorubicin delivery
    Publication . Costa, Emanuel Pedro Rodrigues; Gonçalves, Mara Isabel Jesus
    Cancer continues to be one of the leading causes of death worldwide, with the number of cases expected to rise. Despite advances in medical science, many types of cancer still lack treatments capable of fully eradicating tumors due to their unique characteristics. Chemotherapy remains a common treatment, but it often comes with severe side effects and can sometimes be ineffective. Nanoparticles have gained attention for their ability to enhance cancer treatment by improving drug solubility, targeting tumors more effectively, increasing bioavailability, reducing side effects, and prolonging circulation time. This study focuses on the synthesis and characterization of Laponite®-based nanocomplexes for targeted doxorubicin delivery, aiming to improve therapeutic efficacy while minimizing side effects. The complexes were developed by incorporating polydopamine and polyethyleneimine coatings onto Laponite nanodisks, with additional functionalization using FI PEG-FA for enhanced targeting. The study successfully synthesized and characterized LAP/DOX/PDA(FI-PEG-FA) and LAP/DOX/PEI(FI-PEG-FA) complexes through various physicochemical techniques, including Nuclear Magnetic Resonance, Dynamic Light Scattering, Electrophoretic Light Scattering, and Ultraviolet/Visible spectroscopy. The encapsulation efficiency and loading capacity of DOX were calculated, achieving 99.68% and 28.53%, respectively. The LAP/DOX/PDA(FI-PEG-FA) complex exhibited a diameter of 214.10 nm, a PdI value of 0.45 and a negative surface charge of -16.60 mV. The LAP/DOX/PEI(FI-PEG-FA) complex displayed a diameter of 880.40 nm, a PdI value of 0.41 and a positive surface charge of 20.85 mV. The LAP/DOX/PEI(FI-PEG-FA) complex demonstrated superior effectiveness in sustaining DOX release under physiological conditions compared to the LAP/DOX/PDA(FI-PEG FA) complex. Furthermore, In vitro cytotoxicity assays were performed to assess the impact of these complexes on cancer cell viability, with LAP/DOX/PEI(FI-PEG-FA) demonstrating the most significant reduction in cell viability. At 0.1 µM, the activity is around 60% and drops drastically to about 20% at 2 µM. Cells with the LAP/DOX/PDA(FI-PEG-FA) complex maintained relatively high metabolic activity, ranging from 85% to 100% across all concentrations. The results suggest that these Laponite-based nanocomplexes, particularly those functionalized with FI-PEI-PEG-FA, hold promise as effective vehicles for the controlled release of DOX, with potential applications in targeted cancer therapy. Further studies are recommended to optimize these complexes and assess their performance in vivo.
    2024-11-21Master thesis Embargoed access Show more