Glycyrrhizic Acid‐Based Self‐Targeted Nanomicelles for the Delivery of Gefitinib to PKCα Receptor Overexpressing Cancer Cells

Abstract Glycyrrhizic acid (GCA), also referred to as glycyrrhizin, is a triterpene saponin produced by Glycyrrhiza glabra . GCA has many pharmacological actions, like anti‐inflammatory, antioxidant, and anti‐tumor effects. GCA is generally used as a targeting molecule against protein kinase c alpha (PKC‐α), which is also overly expressed in non‐small cell lung cancer (NSCLC). In this research work, a self‐targeted and self‐assembled nanomicelles system is successfully developed using GCA for the delivery of gefitinib (GEF) for the treatment of lung cancer. The lipid molecule, stearylamine (SA) is conjugated to the GCA to synthesize amphiphilic glycyrrhizic acid‐stearylamine (GCA‐SA) conjugate. The GCA‐SA conjugate is characterized and its critical micelle concentration is determined (100 µg mL −1 ). GEF‐loaded GCA‐SA nanomicelles (GNM) are prepared using the solvent evaporation method and their physicochemical properties are thoroughly investigated. The nanomicelles demonstrate high drug encapsulation efficiency (85%), amorphous drug dispersion, and improved dissolution behavior compared to the free drug. The cytotoxicity studies reveal the high therapeutic efficacy of GNM compared to free GEF, with minimal toxicity observed in the blank nanomicelles group against A549 cells. Overall, these findings suggest that the developed nanocarrier holds great promise for improving the efficacy and selectivity of anti‐cancer agents in the treatment of lung cancer.