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 solu­
bility, poor bioavailability, and high dosage requirements. The current study focuses on addressing these chal­
lenges 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 co-
surfactants, 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.