An Investigation into the Preparation, Characterization, and Therapeutic Applications of Novel Gefitinib/Capric Acid Deep Eutectic Systems

Abstract

Purpose

In this work, we sought to report and fully characterise novel therapeutic deep eutectic systems (THEDESs) formed between Gefitinib (Gef) and capric acid (CA). In addition, we will study the impact of this formulation on solubility and therapeutic efficacy.

Methods

The THEDES were formed using a simple preparation method. Gef and CA were mixed in increasing molar ratios of CA at 40 °C. A phase diagram was used to identify an optimal molar ratio for eutectic formation. Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), and NMR were used to characterise the eutectic systems. Lastly, Cytotoxicity assessments on EGFR-expressing cell lines were conducted to evaluate the therapeutic efficacy of the formulations.

Results

According to the phase diagram, the optimal molar ratio of Gef: CA was found to be G2 (80:20), which facilitates the formation of a homogeneous liquid system at room temperature, confirmed by DSC. FTIR and NMR analysis revealed significant shifts in specific peaks, indicating hydrogen bonding between Gef and CA. More specifically, a downfield shift was observed at protons adjacent to the tertiary nitrogen of the morpholine ring. Gef solubility in CA was enhanced considerably, 30,000 times higher than in aqueous solutions at pH 5. Lastly, according to the cytotoxicity tests, THEDESs, particularly G2 and G3 formulations, have significantly reduced IC50 values compared to individual components, demonstrating a synergistic effect.

Conclusions

The work reports the novel THEDESs of Gef and CA, which enhance Gef solubility and exhibit a synergistic cytotoxic effect against EGFR-expressing cell lines. These findings suggest that THEDESs could offer a promising and facile approach for improving the solubility and therapeutic efficacy of poorly soluble drugs.

Graphical Abstract