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Polymer Based Nano-Formulation of Diindolylmethane with High Oral Bioavailability
Vsevolod Kiselev, Eugenii Klinskiy, Shengmin Lee, Ekaterina Muyzhnek, Alexander Semov and Valery Alakhov
At the present, a high potential of 3,3’-diindolylmethane (DIM) as a new preventive and therapeutic agent in oncology is well established, due to its ability to target multiple components of cancer cell cycle regulation, survival and progression. However, a very low bioavailability of DIM remains the major challenge for its efficient development as novel medicine. In this work, we have developed a polymer based nano-formulation comprising a non-ionic block copolymer, Pluronic F127 that increases oral bioavailability of DIM by almost one order of magnitude, as compared to the presently marketed products such as crystalline DIM and BioResponse DIM. The pharmacokinetic parameters established in the present study revealed that AUC and Cmax of the new formulation dosed at 60 mg/kg were 7.06 ± 0.93 μg â h/mL, and 3.08 ± 0.17 μg/mL, while in the case of crystalline DIM dosed at the same dose AUC and Cmax were 0.97 ± 0.08 μg â h/mL, and 0.18 ± 0.02 μg/mL. BioResponce DIM showed AUC and Cmax of 1.05 ± 0.05 μg â h/mL, and 0.22 ± 0.02 μg/mL, respectively.