Baicalein-loaded nanocochleates for improving oral bioavailability: design, statistical optimization, and in vivo...

Baicalein, a naturally occurring flavonoid, exhibits potent lipoxygenase-inhibitory, anti-inflammatory, and immunomodulatory activities that are beneficial for treating osteoporosis. However, its poor aqueous solubility, low oral bioavailability, and extensive presystemic metabolism restrict its clinical applicability. Thus, the present work aimed to develop baicalein-loaded nanocochleates to improve its oral bioavailability. Baicalein-loaded nanocochleates were prepared from preformed liposomes using the trapping method and further statistically optimized using a 3-factor, 3-level Box-Behnken Design (BBD). The optimized batch showed a particle size of 230.53 ± 7.86 nm, a polydispersity index (PDI) of 0.39 ± 0.01, a zeta potential of -19.07 ± 1.21 mV, and an entrapment efficiency of 93.50 ± 1.32%. Further, DSC and ATR-FTIR results confirmed the successful encapsulation of baicalein within the lipid matrix of nanocochleates, while TEM images revealed elongated, rod-like nanocochleate structures. Importantly, the optimized formulation showed 88.59 ± 1.53% drug release over 24 h compared with baicalein-loaded liposomes (96.10 ± 7.03%), indicating sustained drug release. In vivo oral pharmacokinetic studies demonstrated a 1.49-fold and 11.50-fold increase in C_max and a 2.47-fold and 14.71-fold increase in AUC_0-24 h compared with baicalein-loaded liposomes and plain baicalein, respectively. Collectively, the results suggest that nanocochleates represent a promising carrier system to improve the oral bioavailability of baicalein.