Integrated Extraction, Enrichment, and Formulation of Parthenolide Using Thermoreversible Aqueous Biphasic Systems toward Antitumoral Applications

Abstract

This work reports the development of a thermoreversible aqueous biphasic system (ABS) platform for sustainable extraction and enrichment of parthenolide (PAR), a sesquiterpene lactone with anticancer properties, from Tanacetum parthenium (feverfew). The ABSs were composed of choline-based ionic liquids (Ch-ILs) and Pluronic 17R4, enabling extraction in a monophasic regime at 25 °C and temperature-triggered phase separation at 35 °C. Binodal curves at the two temperatures were determined for multiple Ch-ILs, revealing that ABS formation efficiency correlates with IL salting-out ability and hydration capacity, with choline dihydrogen phosphate, [Ch][DHP], showing the strongest phase separation and choline lactate, [Ch][Lac], the highest PAR extraction yield. Quantum mechanical and molecular dynamics simulations identified the IL polarity through calculated dipole moments as a key factor for extraction efficiency and supported micelle formation in the Pluronic-rich phase. Optimization via improved mixing raised PAR extraction yields to 3.52 mg/g biomass using ABS composed of [Ch][Lac] and 3.42 mg/g using [Ch][Bit]. To evaluate the sustainability of the developed approach, Path2Green metrics were applied, resulting in a score of 0.363. Dynamic light scattering revealed micelle sizes of 100–200 nm with low polydispersity suitable for drug delivery. Cytotoxicity assays on cancer cell lines confirmed the potent antiproliferative activity of ABS-extracted PAR. The proposed platform integrates extraction, enrichment, and formulation in one step.