Nanosuspensions Loaded with Acetogenins: Physical Stability During In Vitro Digestion, Genotoxicity and Cytotoxicity.

Abstract

This study assesses the stability, in vitro bioaccessibility and potential bioavailability, and in vivo genotoxicity and toxicity of polyethylene glycol-soy lecithin (PEGSL-ACG-NSps) or β-cyclodextrin-soy lecithin (βCDSL-ACG-NSps) nanosuspensions (NSps). Both formulations exhibited initial particle sizes below 130 nm and PDI values below 0.3. Under simulated gastrointestinal conditions, PEGSL-ACG-NSps preserved structural integrity, with only a moderate size increase (~239 nm) in the intestinal phase and controlled release of acetogenins (ACGs); in contrast, βCDSL-ACG-NSps destabilized considerably (size > 500 nm) and released ACGs rapidly. Consistently, βCDSL-ACG-NSps achieved higher in vitro bioaccessibility and a potential bioavailability (up to 95% from post-digestion recovery). In contrast, PEGSL-ACG-NSps displayed a more gradual release profile (up to 55%). In vivo toxicity tests in mice showed no significant genotoxic or cytotoxic effects for either formulation, even at high doses. These findings suggest that selecting appropriate food-grade stabilizing polymers is crucial for optimizing NSps for the oral delivery of ACGs as therapeutic agents.