Enhancing the Solubility of Dihomo‐gamma‐Linolenic Acid Using Natural Deep Eutectic Solvents for Human Tumors Therapy Development

Abstract This study investigated the potential of natural deep eutectic solvents (NADES) for dihomo‐ γ ‐linolenic acid (DGLA) solubility. The conductor‐like screening model for real solvents (COSMO‐RS) was used in this study as a computational software tool to predict the relative solubilization ability of 50 different NADES for DGLA. Furthermore, the solubilization mechanisms were examined by analyzing the activity coefficients, sigma profile (σ‐profile), and the excess Gibbs free energy. The results reveal that NADES, consisting of menthol and camphor, Men/Cam (1:1), exhibited the highest capacity (6.352) for DGLA capacity, highlighting its potential for enhanced delivery and application. Furthermore, the σ ‐profile analysis and excess Gibbs free energy calculations confirm strong interaction and miscibility of Men/Cam (1:1) with DGLA. This computational approach offers valuable guidance for selecting the optimal NADES compositions to improve DGLA solubility, potentially advancing cancer therapy strategies and contributing to pharmaceutical science and drug delivery. This is the first study to apply COSMO‐RS in designing and developing a promising therapeutic agent for human tumor treatment.