Polyethylene glycol/soy lecithin-nanosuspensions as carriers of acetogenins: Optimization, characterization, antibacterial and hemolytic activity

Acetogenins (ACGs) are bioactive compounds with high lipophilicity, which limits their pharmaceutical applications. An alternative to increase ACGs solubility is preparing them into suspended nanoparticles in an aqueous solution. The objective of this study was to formulate nanosuspensions (NSps) as ACG carriers by assessing the impact of various soybean lecithin concentrations (SL 5, 10, and 15 mg/mL), polyethylene glycol 6000 (PEG 0.05 %, 0.1 %, and 0.2 %) and dispersion methods (low agitation at 500 rpm, medium agitation at 10,000 rpm and ultrasound) on particle size and polydispersity index (PDI). The experimental data were performed with a response surface analysis to obtain an optimized, validated, and characterized nanosuspension (OPEGSL-ACGs-NSps) and to measure the antibacterial and hemolytic activity. The optimum conditions to get the OPEGSL-ACGs-NSps with spherical-shaped nanoparticles with a size of 100–113.32 nm, a PDI of 0.19, and a zeta potential of −42.14 mV were 15 mg/mL SL and 0.2 % PEG using low agitation (500 rpm) as dispersion method. In addition, the nanoparticles of optimized NSps presented a high entrapment (92.80 %) and encapsulation efficiency (83.33 %); these parameters were confirmed by spectroscopic analysis. Also, 86 % of ACGs were released until 40 h. Moreover, OPEGSL-ACGs-NSps (with 320 μg/mL of ACGs) caused a significant inhibition against E. faecalis(83 %) and L. monocytogenes(86 %); in contrast, they exhibited no hemolytic activity at 250 and 500 μg/mL of ACGs. The new OPEG-ACGs-NSps are an attractive, promising, and cost-effective alternative to improve ACG solubility, and they could also be safe if administered orally or intravenously at low doses.