Fabrication of Curcumin Diethyl γ-Aminobutyrate-Loaded Chitosan-Coated Magnetic Nanocarriers for Improvement of Cytotoxicity against Breast Cancer Cells

Abstract

This study shows the effectiveness of magnetic-guide targeting in the delivery of curcumin diethyl γ-aminobutyrate (CUR-2GE), a prodrug of curcumin (CUR) previously synthesized to overcome unfavorable physicochemical properties of CUR. In this study, chitosan (Ch)-coated iron oxide nanoparticles (Ch-IONPs) were fabricated and optimized using Box–Behnken design-based response surface methodology for delivery of CUR-2GE. Ch was used as a coating material on the nanoparticle surface to avoid aggregation. The optimized condition for preparing Ch-IONPs consisted of using 4 mg Ch fabricated at pH 11 under a reaction temperature of 85 °C. The optimized Ch-IONPs were successfully loaded with CUR-2GE with sufficient loading capacity (1.72 ± 0.01%) and encapsulation efficiency (94.9 ± 0.8%). The obtained CUR-2GE-loaded Ch-IONPs (CUR-2GE-Ch-IONPs) exhibited desirable characteristics including a particle size of less than 50 nm based on TEM images, superparamagnetic property, highly crystalline IONP core, sufficient stability, and sustained-release profile. In the presence of permanent magnets, CUR-2GE-Ch-IONPs significantly increased cellular uptake and cytotoxicity toward MDA-MB-231 with a 12-fold increase in potency compared to free CUR-2GE, indicating the potential of magnetic-field assisted delivery of CUR-2GE-Ch-IONPs for the treatment of triple-negative breast cancer.

Curcumin for Treating Breast Cancer: A Review of Molecular Mechanisms, Combinations with Anticancer Drugs, and Nanosystems

“…Ch-coated iron oxide nanoparticles (Ch-IONPs) were fabricated to deliver a prodrug of CUR, i.e., CUR-diethyl γ-aminobutyrate (CUR-2GE). In the presence of permanent magnets, CUR-2GE-Ch-IONPs significantly increased the cellular uptake of and cytotoxicity toward MDA-MB-231, with a 12-fold increase in potency compared to free CUR-2GE, indicating the potential of magnetic field-assisted delivery of CUR-2GE-Ch-IONPs for the treatment of triple-negative breast cancer [ 91 ]. Injectable and in situ-formable thiolated chitosan-coated liposomal hydrogels were studied as CUR carriers for the prevention of in vivo BC recurrence [ 92 ].…”