Encapsulation of Annona muricata Acetogenins in Self-Nanoemulsifying Drug Delivery Systems (SNEDDSs): Controlled Release and Antiproliferative Activity in MC-38 Colon Cancer Cells

Acetogenins (ACGs) are bioactive compounds typically found in the Annonaceae family, such as soursop (Annona muricata), and have demonstrated strong antineoplastic effects at very low doses across different cancer cell lines. However, their poor water solubility limits their bioavailability and bioactivity. This research aimed to prepare and evaluate self-nanoemulsifying drug delivery systems (SNEDDSs) to improve the solubility and efficacy of ACGs against colon cancer cells. The results indicated that ACGs could be effectively dissolved in medium-chain triglycerides, mainly composed of caprylic acid, reaching a concentration of 20 mg/mL. Pseudoternary phase diagrams were used to identify spontaneous nanoemulsification zones using Cremophor® EL/Tween 80 as surfactants and polyethylene glycol as a cosurfactant. The resulting nanoemulsions exhibited droplet sizes ranging from 14.6 to 50.18 nm and polydispersity indices between 0.04 and 0.18. In vitro tests simulating gastrointestinal conditions showed the stability of nanoemulsion particle size for 105 min in a simulated small intestine environment. An in vitro release assay revealed a 92.2% release of ACGs incorporated into SNEDDSs after 7 h. Finally, cell-based assays demonstrated that ACG-loaded nanoemulsions exerted cytotoxic effects on MC-38 colon cancer cells, with an IC50 of 16.32 μg/mL. These findings support the potential of SNEDDS-encapsulated ACGs as an effective strategy for colon cancer therapy.