Objective To prepare lentinan-buddleoside self-assembled nanoparticles (Len-Bud-SANs), and evaluate investigate its physicochemical properties, oral pharmacokinetic behavior and acute toxicity. Methods Len-Bud-SANs were prepared by self-assembled method. Envelopment efficiency, drug loading and particle size were employed as indicators, single factor experiments combined with Box-Behnken design-response surface method (BBD-RSM) were used to obtainoptimal prescriptions of Len-Bud-SANs. The appearance of Len-Bud-SANs was observed by transmission electron microscope (TEM) was, crystal form of Len-Bud-SANs powder was analyzed by X-ray powder diffraction (XRPD). Molecular simulation docking and Fourier transform infrared spectroscopy (FTIR) were used to study the binding mechanism between lentinan and buddleoside. The solubility and drug release behavior of Len-Bud-SANs were determined in phosphate buffer solution (PBS) at pH 2.0 and pH 6.8. SD rats in each group were administered intragastrically with buddleoside suspension and Len-Bud-SANs powder, then buddleoside concentration in plasma was analyzed by HPLC method, and main pharmacokinetic parameters were calculated. Safety evaluation of Len-Bud-SANs powder was performed by indicators of body weight, food intake, thymus index and spleen index. Pathological conditions of the important organs were observed by hematoxylin-eosin (HE) staining. Results Optimal formulation of Len-Bud-SANs: mass fraction of lentinan was 0.39%, preparation temperature was 65.00 ℃, and preparation time was 1.50 h. Envelopment efficiency, drug loading, particle size and ζ potential were (88.57 ±0.83)%, (8.02 ±0.11)%, (57.54 ±4.90) nm and (−32.10 ±1.36) mV, respectively. Microscopic appearance of Len-Bud-SANs was spherical, and buddleoside existed as an amorphous form in Len-Bud-SANs powder. Solubility of Len-Bud-SANs in phosphate buffer solution of pH 2.0 and pH 6.8 was increased to 59.89 times and 42.95 times, and cumulative release rate were increased to 90.80% and 91.73%, respectively. Drug release behavior of Len-Bud-SANs conformed to Weibull model. Oral pharmacokinetic results showed that t_1/2 of Len-Bud-SANs was increased to (4.45 ±0.80) h, C_max and AUC_0-t were increased to 3.00-fold and 5.60-fold. Compared with the blank group, there was no significant change in body weight, food intake, thymus index, spleen index and pathology of important organs in the Len-Bud-SANs group. Conclusion Len-Bud-SANs significantly promoted oral absorption of buddleoside effectively, and no obvious toxicity was observed, which laid the foundation for subsequent research and development.

buddleoside  /  self-assembled  /  nanoparticles  /  Box-Behnken response surface design method  /  solubility  /  drug release behavior  /  pharmacokinetic  /  bioavailability  /  acute toxicity