Nanoparticle platforms for encapsulation of therapeutic deep eutectic systems to target colorectal cancer cells

Given the growing interest in deep eutectic systems (DES) for their remarkable physicochemical and biological properties, and their alignment with green chemistry principles, we explored their therapeutic potential against colorectal cancer (CRC) in this study. The reported promising selective toxicity of therapeutic deep eutectic systems (THEDES), combining a terpene (menthol, thymol, perillyl alcohol and limonene) with ibuprofen (Ibu), towards CRC cells, have pushed them forward as potential alternative or complementary therapeutics towards CRC. These systems are considered THEDES since they are eutectic systems with a pharmaceutic ingredient as part of its composition. To leverage THEDES viability as CRC therapeutics, different drug delivery systems (DDS), based on poly (lactic-co-glycolic acid) nanoparticles (PLGA-NPs), liposomes (LPS) or niosomes, were explored to ensure THEDES accumulation in cancer sites. For that, nanoprecipitation, microfluidics and thin-film hydration methods were used, respectively, to produce THEDES encapsulated DDS. From the different DDS produced, LPS presented the most promising results regarding size (200 nm), monodispersity, and negative zeta potential averaging −30 mV. These results indicate LPS as a stable, monodispersed particle suspension suitable for cancer-related applications, hence, these NPs were selected for further assessments. The obtained THEDES-LPS revealed expected morphology upon electron microscopy observation (TEM), a 10 % release after 96h, and a maximum encapsulation efficiency (EE%) of 41 % obtained for limonene (Lim):Ibu (4:1). All THEDES-LPS revealed antiproliferative activity towards HT-29 cells which envisage LPS as a DDS for THEDES towards CRC.