Development of a self-nanoemulsifying drug delivery system of diindolylmethane for enhanced bioaccessibility, bioavailability and anti-breast cancer efficacy

Diindolylmethane (DIM), a bioactive compound rich in cruciferous vegetables, has been well known for its health benefits, including anticancer properties. However, its clinical utilization has been limited due to its low solubility, poor bioavailability, and high dosage requirements. The current study focuses on addressing these challenges by developing a self-nanoemulsifying drug delivery system (SNEDDS) for DIM to improve its delivery and therapeutic efficacy. Through careful optimization of various combinations of oils, surfactants, and cosurfactants, an ideal self-nanoemulsion formulation was achieved utilizing medium-chain triglyceride (MCT) oil, Tween 80, and PEG400 in a ratio of 20:60:20 (w/w/w), respectively. The resulting SNEDDS demonstrated favorable physicochemical properties, including stability and optimal particle size. The DIM-loaded SNEDDS (DIM-SNEDDS) exhibited a particle size of 17.99 +/- 8.92 d. nm, a zeta potential of -15.4 +/- 5.93 mV, and a polydispersity index (PDI) of 0.15 +/- 0.07, signifying uniformly distributed droplets with spherical morphology. DIM-SNEDDS showed a significantly higher DIM release rate compared to the DIM suspension at pH 1.2 and 6.8 buffers in vitro. Importantly, DIM-SNEDDS improved the bioaccessibility of DIM by over 40 % and bioavailability by 8.27 times compared to DIM in MCT oil. Moreover, DIM-SNEDDS showed significantly higher inhibition of breast tumor growth, progression, and lung metastasis in a murine mammary tumor model over native DIM treatment. Our findings highlight DIM-SNEDDS as a promising drug delivery system, potentially enhancing the therapeutic effect of DIM in breast cancer management.