Wheatgrass-Tulsi Self-Emulsifying Drug Delivery System (WT-SEDDS): Preclinical Evaluation Of Synergistic Anticancer Activity

Breast cancer remains a significant global health concern, ranking as the second leading cause of cancer-related mortality among women. The increasing incidence necessitates the development of more efficacious therapeutic strategies. This study evaluates the potential of a novel Wheatgrass-Tulsi Self-Emulsifying Drug Delivery System (WT-SEDDS) as an anticancer agent through comprehensive in vitro and in vivo investigations. The antioxidant capacity of WT-SEDDS was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay at concentrations ranging from 50 to 400 µg/mL. Cytotoxicity was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells and predipocyte-derived mouse embryonic fibroblasts (normal cell line) at concentrations of 12.5-100 µg/mL. Antimitotic activity was investigated using earthworm regeneration model at WT-SEDDS concentrations of 100, 500, and 1000 µg/mL. Acute oral toxicity was assessed following OECD Guideline 425 [23]. In vivo studies utilized a 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer model in Sprague Dawley rats. WT-SEDDS and tamoxifen treatments were compared for their effects on tumor incidence, volume, and burden. Hematological parameters (hemoglobin, red blood cell count) and oxidative stress markers (superoxide dismutase, reduced glutathione, malondialdehyde) were quantified. Histopathological analysis was performed to confirm the therapeutic efficacy. Results demonstrated that WT-SEDDS exhibited significant antioxidant, cytotoxic, and antimitotic properties in vitro, with no acute oral toxicity observed. In vivo, WT-SEDDS treatment significantly reduced tumor progression and modulated hematological and oxidative stress parameters comparable to tamoxifen. Histopathological findings corroborated the therapeutic potential of WT-SEDDS against DMBA-induced mammary carcinogenesis. This study provides compelling evidence for the anticancer efficacy of WT-SEDDS, warranting further investigation as a potential therapeutic agent for breast cancer management.