Selective terpene based therapeutic deep eutectic systems against colorectal cancer

Area of Science:

• Pharmaceutical Science
• Oncology
• Materials Science

Background:

• Colorectal cancer (CRC) is a leading cause of cancer-related deaths globally.
• Inflammation is closely linked to cancer development and progression, making its reduction a key therapeutic strategy.
• Deep eutectic systems (DES) offer a novel approach for drug delivery and formulation.

Purpose of the Study:

• To develop and evaluate novel therapeutic deep eutectic systems (THEDES) for colorectal cancer (CRC) treatment.
• To investigate the anti-CRC potential of THEDES combining terpenes with nonsteroidal anti-inflammatory drugs (NSAIDs).
• To assess the physico-chemical properties, bioavailability, and bioactivity of these new THEDES.

Main Methods:

• Synthesis of THEDES by combining terpenes (safranal, menthol, linalool) with NSAIDs (ibuprofen, ketoprofen, flurbiprofen).
• Evaluation of THEDES' anti-cancer activity against CRC cells, including cytotoxicity, anti-proliferative effects, and apoptosis induction.
• Assessment of changes in drug solubility, permeability, and reactive oxygen species (ROS) production.

Main Results:

• Safranal:ibuprofen (3:1), safranal:ibuprofen (4:1), and menthol:ibuprofen (3:1) demonstrated selective cytotoxicity against CRC cells.
• Menthol:ibuprofen (3:1) exhibited anti-proliferative effects via cell membrane disruption, reduced ROS production, and induced apoptosis.
• Safranal:ibuprofen formulations induced apoptosis via caspase-3 activation and enhanced ibuprofen permeability and solubility, improving bioavailability.

Conclusions:

• THEDES formulations, particularly those with ibuprofen, show significant therapeutic potential against colorectal cancer.
• These systems offer a promising strategy for developing more effective and potentially less toxic cancer therapies.
• DES represent a sustainable and cost-effective platform for pharmaceutical innovation in cancer treatment.