Evaluation of Drug Effectiveness and Controlled Release Profiles of Clay Minerals Loaded with Anti-Carcinogenic Agent as a Drug Delivery System on Leukemia.

Abstract

Objective: Myeloid leukemia is a stem cell disease with high mortality due to the challenges of high-dose treatments and side effects. Innovative nanoparticle drug delivery systems are being explored to enhance efficacy and tissue-targeted therapy. This study investigates the potential of Bentonite (BNT)-based nanoparticles (NPs) as drug carriers for azacitidine (AZA) in treating THP-1 and K562 myeloid leukemia (AML) cell lines, aiming to improve drug stability, bioavailability, and therapeutic efficacy while ensuring controlled release.

Material and method: Bentonite clay morphology was analyzed using Scanning Electron Microscopes. The BNT-AZA combination was tested in THP-1 and K562 cell cultures via in vitro proliferation tests, CCK-8 assays, and drug release tests with dialysis membranes. Apoptosis and internalization were evaluated using Annexin V-FITC and fluorescence methods, respectively.

Results: The BNT-AZA exhibited controlled release over 8 hours, with 50% released within 2 hours, 90% by the 4th hour, and prolonged release beyond 8 hours. This profile reduces side effects while increasing efficacy in target cells. Bentonite demonstrated significant drug-loading capacity, controlled release, and tumor-targeting capabilities. At concentrations of 10, 25, 50, and 100 µg/mL, BNT showed dose-dependent antiproliferative effects, maintaining low cytotoxicity at lower concentrations. The combination of azacytidine and bentonite exhibited a synergistic effect in inhibiting cell proliferation, with significant decreases in cell viability in the 1 µM azacytidine + 10 µg/mL bentonite, 5 µM azacytidine + 10 µg/mL bentonite, and 10 µM azacytidine + 10 µg/mL bentonite groups compared to the controls. The combination of 1 µM AZA with 10 µg/mL BNT achieved similar efficacy to 10 µM AZA alone, suggesting a potential for dose reduction and improved safety.

Conclusion: BNT nanoparticles are promising carriers for AZA, enhancing targeted delivery, reducing side effects, and potentially lowering the required dose for leukemia treatment. These findings support further investigation into the clinical application of BNT-AZA in hematologic cancers.