Chrysin-loaded folate conjugated PF127-F68 mixed micelles with enhanced oral bioavailability and anticancer activity...

Chrysin (CH), a phytoconstituent has numerous pharmacological activities including anticancer activity. However, CH suffers from a drawback of poor aqueous solubility and in turn poor bioavailability limiting its clinical utility. In this work CH loaded folate-conjugated pluronic PF127-pluronic F68 mixed micelles were prepared with an objective to augment oral bioavailability and cytotoxicity of CH in human breast cancer cell line MCF-7 by active targeting mechanism. Folate-conjugated PF127 was synthesized and used for preparation of CH-MM. Optimized batch (using factorial design) of CH-MM was characterized by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), atomic force microscopy (AFM), in vitro CH release, in vivo study, and in vitro cell line study. FTIR study suggested encapsulation of CH into the micelle core. CH-MM showed controlled release of CH releasing higher amount (2.5 fold) in 24 h when compared to CH alone (A-CH). Further significant increase in C_max (2 fold) and AUC_0-∞ (3 fold) for CH-MM when compared to A-CH suggested significant improvement in oral bioavailability of CH. Additionally, CH-MM showed 5 fold reduction in GI₅₀ value of CH when tested in MCF-7 cells reducing GI₅₀ value of CH significantly. CH-MM can serve as a platform carrier system for active targeting of BCS class II molecules with potential anticancer activity.