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

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Drug Delivery Systems

Background:

• Oral delivery of acetogenins (ACGs) is challenging due to stability and bioavailability issues.
• Nanosuspensions (NSps) offer a promising approach to enhance ACG delivery.
• The choice of stabilizing excipients significantly impacts NSps performance.

Purpose of the Study:

• To evaluate the stability, in vitro bioaccessibility, potential bioavailability, and in vivo toxicity of two NSps formulations for ACG oral delivery.
• To compare polyethylene glycol-soy lecithin (PEGSL-ACG-NSps) and β-cyclodextrin-soy lecithin (βCDSL-ACG-NSps).
• To determine the impact of stabilizing polymers on ACG release and NSps performance.

Main Methods:

• Characterization of NSps particle size and polydispersity index (PDI).
• Assessment of NSps stability and acetogenin (ACG) release under simulated gastrointestinal conditions.
• In vitro bioaccessibility and potential bioavailability studies.
• In vivo genotoxicity and cytotoxicity assessments in mice.

Main Results:

• Both PEGSL-ACG-NSps and βCDSL-ACG-NSps had initial particle sizes <130 nm and PDI <0.3.
• PEGSL-ACG-NSps maintained structural integrity with controlled ACG release, while βCDSL-ACG-NSps destabilized rapidly.
• βCDSL-ACG-NSps showed higher in vitro bioaccessibility (up to 95%) and potential bioavailability, whereas PEGSL-ACG-NSps demonstrated a more gradual release (up to 55%).
• No significant genotoxic or cytotoxic effects were observed for either formulation in vivo.

Conclusions:

• The selection of food-grade stabilizing polymers is critical for optimizing NSps for oral ACG delivery.
• PEGSL-ACG-NSps demonstrate superior stability and controlled release, suggesting potential for therapeutic applications.
• While βCDSL-ACG-NSps show higher initial bioaccessibility, their instability may limit long-term therapeutic efficacy.