Inhalable TPGS/DPPC Micelles Coloaded with Curcumin and Icariin for Targeted Lung Cancer Therapy

Lung cancer, particularly NSCLC, poses a major therapeutic challenge due to drug resistance and the poor aqueous solubility of chemotherapeutic agents, limiting treatment efficacy. This study investigates inhalable micelles for the codelivery of curcumin (CUR) and icariin (ICA), two hydrophobic bioactive compounds with anticancer potential, as a targeted therapeutic approach for NSCLC. The optimized micellar formulation (9:1 TPGS/DPPC) yielded nanomicelles (∼18 nm) with high encapsulation efficiency (∼90%) and a zeta potential of -1.24 mV, demonstrating stability for pulmonary administration. In vitro cytotoxicity studies demonstrated enhanced anticancer activity of CUR- and ICA-loaded micelles against A549 lung cancer cells (IC₅₀ = 3.0 μg/mL), lower than doxorubicin (30 μg/mL), suggesting enhanced cytotoxic potential. Additionally, DPPH assays confirmed that encapsulation preserved curcumin's functionality. Aerosolization studies demonstrated a high fine particle fraction (67 ± 3%) and emitted fraction (95 ± 1.0%), confirming the micelles' suitability for deep lung deposition and effective pulmonary drug delivery. These findings highlight the potential of CUR- and ICA-loaded micelles as an inhalable NSCLC treatment, requiring further preclinical investigation.