Preparation and evaluation of kaempferol–phospholipid complex for pharmacokinetics and bioavailability in SD rats

• We successfully prepared and evaluated kaempferol–phospholipid complex.
• A UHPLC–MS/MS method was developed and fully validated to determine the concentration of KP in vivo.
• The comparison of bioavailability between kaempferol and kaempferol–phospholipid complex were carried out.

As one of the dietary flavonoids, kaempferol (KP) has been well known to show strong anti-oxidative effect along with other biological properties. However, the oral bioavailability of KP is relatively low due to its poor solubility. In this study, we intended to increase the solubility and bioavailability of KP by preparing kaempferol–phospholipid complex (KP–PC). The KP–PC's physicochemical properties were characterized in terms of infrared spectroscopy (IR), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD), water/n-Octanol solubility and in vitro dissolution. KP–PC exhibited higher solubility and dissolution rate than KP, indicating a significant improvement in hydrophilicity. A UPLC–ESI–MS/MS method was developed and validated for the determination of KP in Sprague-Dawley (SD) rat plasma, so as to investigate the oral bioavailability of KP–PC versus KP. Results showed that Cmax and AUC0–48 h of KP from the complex (Cmax: 3.94 ± 0.83 μg/mL, AUC0–48 h: 57.81 ± 9.43 mg/L h) were higher than that of KP (Cmax: 1.43 ± 0.21 μg/mL, AUC0–48 h: 13.65 ± 3.12 mg/L h). This research indicated that phospholipid complex (PC) might be one of the suitable approachs to improve the oral bioavailability of KP and other poor-solubility flavonoids.

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