Rubén Ricardo Córdova-Espíritu

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.

Camptothecin (CPT) is a natural alkaloid with potent antiproliferative activity, mediated by the inhibition of Topoisomerase I (Topo I), an essential enzyme for deoxyribonucleic acid (DNA) replication. However, its clinical application has been limited by low solubility and the instability of the lactone ring under physiological conditions, both of which decrease its efficacy. Semi-synthetic analogs such as irinotecan (CPT-11) and topotecan (TPT) have been developed and approved for the treatment of various types of cancer; however, challenges related to drug resistance and side effects continue to arise. Therefore, nanomedicine and nanoparticle-based delivery systems, including nanoemulsions, liposomes, and antibody–drug conjugates (ADCs), emerge as promising strategies to improve the stability, bioavailability, and effectiveness of CPT, despite significant challenges such as scalability, pharmacokinetic variability, and regulatory requirements. This review discusses recent advances in CPT, its analogs, and these delivery platforms, highlighting its potential to optimize cancer therapy and reduce toxicity while outlining translational challenges such as scalability, pharmacokinetic variability, and regulatory requirements.