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

Jagadish, Natesh and Yahya, Mukhlis and Sumathy, Ramasamy and Priya, Mondal and Bhavjot, Kaur and Syed Musthapa, Meeran (2024) Development of a self-nanoemulsifying drug delivery system of diindolylmethane for enhanced bioaccessibility, bioavailability and anti-breast cancer efficacy. Journal of Drug Delivery Science and Technology, 93. pp. 1-17.

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Bioaccessibility Bioavailability Breast cancer Diindolylmethane Self-nanoemulsifying drug delivery system (SNEDDS)
Subjects: 500 Natural Sciences and Mathematics > 10 Plants
500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 18 Phytochemistry
600 Technology > 01 Medical sciences > 09 Human Physiology
Divisions: Dept. of Biochemistry
Depositing User: Somashekar K S
Date Deposited: 06 Mar 2025 06:12
Last Modified: 06 Mar 2025 06:12
URI: http://ir.cftri.res.in/id/eprint/19216

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