RESUMO
To improve the water solubility of daidzein, solid inclusion complexes of daidzein with two amino-modified β-cyclodextrins (ACDs), i.e., mono-6-amino-6-deoxy-β-cyclodextrin (NCD) and mono-6-ethylenediamino-6-deoxy-β-cyclodextrin (ENCD), were prepared by the saturated solution method in water under the preparation conditions as follows: the ratio of daidzein/ACD was 3∶1 and the stirring time was 72 h (83% and 67% yields, respectively).The formation of two inclusion complexes was confirmed by x-ray diffractometry (XRD) and themogravimetric (TG) analysis.The inclusion stoichiometry of the inclusion complexes was 1∶1 from the Job plot and their complexation stability constants (KS) were 899.2 and 203.8 L/mol from fluorescence titration, respectively.After formation of inclusion complexes with NCD and ENCD, the water solubility of daidzein was dramatically raised from 8.31 μg/mL to 15.2 and 13.2 mg/mL at 25℃, increasing by 1800-fold and 1500-fold.
RESUMO
OBJECTIVE: To prepare and evaluate resveratrol-loaded mesoporous silica nanoparticles modified by amino (NH2-MSN-RES) to improve the bioavailability of resveratrol. METHODS: Mesoporous silica nanoparticles modified by amino (NH2-MSN) were synthesized by the modified Stober method. The structure of the nanoparticles were analyzed and characterized by FT-IR, Malvern particle size analyzer, and TEM. By introducing the innovative preparation process of repeated saturated solution adsorbing method, RES was encapsulated into NH2-MSN in larger amount. Dialysis bag method was used to investigate the in vitro drug release characteristics and MTT method was used to investigate the cytotoxicity on Caco-2 cells. The transport ability of the carrier was investigated by the Caco-2 cells monolayer model. Finally, the pharmacokinetics of NH2-MSN-RES was studied in rats. RESULTS: The particle size distribution of NH2-MSN was uniform with an average value of (98.4±2.8) nm, and the Zeta potential was (13.2±1.8) mv. Within the scope of 0-20 μg·mL-1, NH2-MSN had no obvious toxicity on Caco-2 cells. After 8 times of repeated adsorption, the drug loading of NH2-MSN-RES reached up to (19.26±2.51)%. In the drug release experiment, the cumulative release quantity of NH2-MSN-RES was 73.3% within 48 h, indicating sustained-release characteristics. NH2-MSN-RES had good ability of transmembrane transport in the Caco-2 cell monolayer model, and the two-way apparent permeability coefficient (Papp) was much larger than the RES solution. In the pharmacokinetic study, RES solution complied with one-compartment model, whereas NH2-MSN-RES complied with two-compartment model, indicating that the carrier changed the pharmacokinetic characteristics of RES. The AUC0-∞ of NH2-MSN-RES was 2.58-fold of that of RES solution, what's more, the t1/2, tmax, and ρmax of NH2-MSN-RES were significantly greater than those of RES solution. CONCLUSION: NH2-MSN is synthesized by modified Stober method successfully. Repeated saturated solution adsorbing method could effectively improve the drug loading. NH2-MSN-RES improves the bioavailability of RES prominently. NH2-MSN will be a promising nano-material for oral drug delivery carrier.