Host–guest interaction between 20(S)-protopanaxatriol and three polyamine-modified β-cyclodextrins: preparation, characterization, inclusion modes, and solubilization

Abstract

20(S)-protopanaxatriol (PPT) is a kind of tetracyclic triterpenoid, which is found in the roots of ginseng. It is well known as a potential herbal medicine or healthcare product. However, given its poor water solubility, its application has been limited. In this study, we successfully synthesized a novel mono-[6-(N,N-bis(3-aminopropyl)ethylenediamine)-6-deoxy]-β-cyclodextrin. We prepared inclusion complexes of PPT with three polyamine-modified β-cyclodextrins (CDs) (H1, H2, and H3) of different lengths by the coprecipitation method, aiming at enhancing the aqueous solubility of PPT. The host–guest inclusion complexes of H1, H2, and H3 with PPT were characterized via 1H NMR, XRD, FT-IR spectra, and SEM technology, and the inclusion modes were analyzed by 2D ROESY. The stability constant (Ks), inclusion ratios, and solubility of H1, H2, and H3 with PPT were determined via the phase solubility method. The stability constants (K1:1) were found to be 182.6, 94.2, and 524.4 M−1 for H1/PPT, H2/PPT, and H3/PPT inclusion complexes, with AL-, AN-, and BS-type curves, respectively. That is, when the stoichiometric ratio was 1:1, H3 (with longest-length chain) displayed the strongest binding ability with PPT. The host–guest size/shape-fit relationship and hydrogen bond interaction play a role in improving the stability of H1/PPT, H2/PPT, and H3/PPT inclusion complexes. Through complexation with H1, H2, and H3, the apparent solubility of PPT was obviously increased from the initial value of 0.062 mg/L to 5.1, 3.0, and 7.5 g/L, respectively. Among the three CDs, the solubilization effect of PPT with H3 was the best. Furthermore, H1/PPT, H2/PPT, and H3/PPT inclusion complexes exhibited some activity in inhibiting LPS-induced nitric oxide (NO) generation in macrophages. This satisfactory aqueous solubility and higher stability of H1/PPT, H2/PPT, and H3/PPT inclusion complexes should be possibly useful for its utilization as a herbal medicine and healthcare product.