Development and Optimization of Curcumin-Loaded Citric Acid Functionalized Multi-Walled Carbon Nanotubes for Enhanced Breast Cancer Treatment Using Design of Experiment

Abstract

Curcumin, a natural polyphenol derived from turmeric, holds significant promise for breast cancer treatment due to its diverse pharmacological properties, which include antioxidant, neuroprotective, anti-inflammatory, and anti-amyloid effects. However, its clinical application is limited by its poor solubility and low bioavailability. The objective of this study is to develop a novel drug delivery system using citric acid (CA)-functionalized carboxylated (COOH) Multi-Walled Carbon Nanotubes (MWCNTs) to enhance the solubility and bioavailability of curcumin for effective breast cancer treatment. The formulation of curcumin-loaded MWCNT-COOH-CA was optimized using a Box-Behnken design. The characterization of curcumin-loaded MWCNT-COOH-CA incorporated evaluations of particle size, zeta potential, and % entrapment efficiency. Furthermore, the formulation underwent in vitro release and cytotoxicity assessments. The optimal formulation exhibited a particle size of 371 nm, a zeta potential of -25.2 mV, and an entrapment efficiency of 77.86%. In vitro release study demonstrated a pH-dependent release pattern, with enhanced release under acidic conditions simulating the tumor microenvironment, which showed a cumulative release of 93.48% at pH 5.5 as compared to 91.24% at pH 7.4 at the 24-hour time point. The formulated product exhibited significant cytotoxic activity against MCF7 breast cancer cells, with an IC₅₀ value of 30.82 µg/mL, and demonstrated efficient cellular uptake. The novel curcumin-loaded MWCNT-COOH-CA demonstrated potential as an efficacious and targeted approach for the treatment of breast cancer.