Bioflavonoid hesperetin overcome bicalutamide induced toxicity by co-delivery in novel SNEDDS formulations: Optimization, in vivo evaluation and uptake mechanism.

Abstract In the present study, we designed Bicalutamide (BCT) and Hesperetin (HSP) co-loaded self nano-emulsifying drug delivery system (SNEDDS) to encounter the problem of BCT induced toxicity, low solubility, and bioavailability. Optimized BCT-HSP SNEDDS would produce an emulsion of globule size 30.84 ± 1.24 nm with a high encapsulation efficiency of BCT (91.29%) and HSP (88.19%), and showed rapid drug release. DPPH assay confirmed the retention of antioxidant potential of HSP in SNEDDS. DCFH-DA confirmed intense green fluorescence in HSP treated groups due to the generation of reactive oxygen species. Thermogravimetric analysis showed the change in the polymorphic form of BCT. After 14 days of sub-acute toxicity study, no significant increase (p > 0.05) in the hepatotoxicity markers was observed but BCT-HSP SNEDDS significantly decreased (p  0-t of BCT (1.23 fold) and HSP (3.42 fold) than aqueous suspension in male Sprague-Dawley rats. The BCT-HSP SNEDDS were absorbed by clathrin-mediated endocytosis and lymphatic transport absorption pathway. Our results proposed that the co-delivery approach may be useful for in vivo management of prostate cancer.