Silk Fibroin Nanoparticles as a Drug Delivery System of 3,3'-Diindolylmethane with Potential Antiobesogenic Activity

Obesity is a global disease characterized by excessive lipid accumulation in the adipose tissue. There is an urgent need to explore alternative compounds to treat obesity. Low-molecular-weight compounds from plants, like 3,3'-diindolylmethane (DIM), are emerging as potential alternatives for obesity treatment. In this work, DIM is encapsulated into silk fibroin nanoparticles (SFNP) to evaluate the antiobesogenic potential. The obtained spherical-like SFNPs have a particle size between 165 and 200 nm, a polydispersity index between 0.11 and 0.15, and a zeta potential from -27 to -37 mV. DIM does not modify the nanoparticle shape but changes the secondary structure of fibroin and generates smaller nanoparticles (145 nm). DIM-loaded SFNP (SFNP-DIM) enhance their antioxidant capacity by 4.4-fold compared to SFNP. SFNP-DIM does not show cytotoxicity on white-like adipocytes, unlike 3T3-L1 preadipocytes, where cell viability decreased in a concentration-dependent manner. The SFNP-DIM treatment (5 μM, 0.03 mg SFNP mL^-1) does not modify the morphology of white-like adipocytes. It produces an apparent augmentation in the size and number of intracellular lipid droplets and increases by 2.18 ± 0.4-fold of triglyceride content. These findings demonstrated that SFNPs could be a potential delivery system of DIM, suggesting a potential therapeutic agent for treating obesity.