Fabrication of Nanosuspensions to Improve the Oral Bioavailability of Total Flavones from Hippophae rhamnoides L. and their Comparison with an Inclusion Complex.

ABSTRACT

The aim of this work was to increase the solubility and oral bioavailability of isorhamnetin, kaempferol, and quercetin in the total flavones of Hippophae rhamnoides L. (TFH) by preparing their nanosuspensions (NSs) and an inclusion complex. Based on the particle size and zeta potential, P407, Soluplus, SDS, PEG-6000, and HP-ß-CD were selected as stabilizers. TFH NSs and a TFH/HP-ß-CD inclusion complex were prepared, and their morphology, crystallinity, molecular interactions, and cytotoxicity were investigated. Furthermore, the saturation solubility, dissolution, and pharmacokinetics of the three flavonoids in the TFH, TFH NSs, and TFH/HP-ß-CD inclusion complex were compared. The five obtained TFH NSs were physically stable, and their particle sizes were all below 200 nm. The solubility and dissolution of the three active components were obviously enhanced by the formation of the TFH NSs and TFH/HP-ß-CD inclusion complex. Correspondingly, the oral bioavailability of isorhamnetin, kaempferol, and quercetin increased up to 4.11-, 3.85-, and 6.73-fold, respectively, in the TFH NSs and 2.89-, 3.71-, and 9.51-fold, respectively, in the TFH/HP-ß-CD inclusion complexes compared to those in the raw TFH. In brief, both NSs and inclusion complexes can improve the oral bioavailability of the three flavonoids in TFH. Taking the drug loading and the stable ratio of the multiple components into consideration, the NSs is a more promising strategy than the inclusion complex for increasing the oral bioavailability of multiple water-insoluble components in herbal extracts. Graphical abstract.