Enhancing Curcumin Performance via PVP K30 Solid Dispersion: Synergistic Potential in Combination with Conventional Chemotherapeutic Agents in NSCLC Cells

Curcumin (CUR) has shown promising anticancer activity against non-small cell lung cancer (NSCLC), but its poor biopharmaceutical properties limit its applications. This study aimed to optimize a solid dispersion of CUR with polyvinylpyrrolidone K30 (PVP K30) to enhance its biopharmaceutical properties and to evaluate its ability to enhance cytotoxic activity of conventional chemotherapeutic drugs (Afatinib, Cisplatin, and Metformin) in A549 NSCLC cells. Solid dispersions (CUR:PVP K30 at ratios of 1:9, 1:12, and 1:15) were prepared using four different protocols. The 1:9 solid dispersion obtained with Protocol 4 exhibited the highest thermodynamic solubility (> 14,000-fold increase; 408.00 µg/mL) and an improved intrinsic dissolution rate. Furthermore, the characterization of the solid dispersions by DSC, FTIR and PXRD confirmed the formation of amorphous solid dispersions, which are suggested to be stable according to the thermal stress study at 70°C. Cytotoxicity was assessed via MTS assay after 48 h. The Half-maximal inhibitory concentration (IC₅₀) values were 0.03, 0.04, 3.30 and 0.13 mg/mL for Afatinib, Cisplatin, Metformin and CUR:PVP K30 (1:9, protocol 4), respectively. The combination of conventional chemotherapeutic drugs with the 1:9 CUR:PVP K30 formulation at Minimum effective concentration (MEC) or IC₅₀ significantly enhanced cytotoxicity. Analysis of the combination index (CI) revealed synergistic interactions, as values less than 1 (CI < 1) were obtained for all combinations. These findings demonstrate that the use of solid dispersions significantly improves the solubility of CUR, potentially offering a promising strategy for enhancing the in vitro cytotoxic activity of conventional chemotherapeutic agents.