Maleimide-modified limonin nanoparticles:Preparation,characterization and its oral pharmacokinetics study
Objective To prepare maleimide-modified limonin nanoparticles(Mal-Lim-NPs),characterize its physicochemical properties,and study its oral pharmacokinetic behavior.Methods Single factor experiments combined with Box-Behnken response surface design method(BBD-RSM)was used to gain optimal prescriptions of Mal-Lim-NPs,and its lyophilized powder was prepared.Crystal form of limonin in lyophilized powder of Mal-Lim-NPs was analyzed by X-ray powder diffraction(XRPD),and microscopic appearance was observed by transmission electron microscope(TEM).Solubility and drug release rate of Mal-Lim-NPs in pH 2.0,5.0,6.8 phosphate buffers(PBS)were determined.SD rats in each group were administered intragastrically with limonin and Mal-Lim-NPs,respectively,blood drug concentration-time curve was plotted,and main pharmacokinetic parameters was also calculated.Results Optimal prescriptions of Lin-Mal-NP:Mal-PEG-PLA to limonin dosage ratio was 7.5∶1,water phase volume was 35 mL and ultrasonic time was 13 min.Average envelopment efficiency,drug loading,particle size and ζ potential were(81.63±1.30)％,(9.32±0.24)％,(171.56±6.63)nm and(-16.60±0.92)mV,respectively.The crystalline state of limonin maybe changed in Mal-Lim-NPs lyophilized powder.Microcosmic appearance of Mal-Lim-NPs was still nearly spherical after dissolved by water.The release behavior of Mal-Lim-NPs in pH 2.0,5.0,6.8 PBS were in accordance with Weibull model.The tmax of Mal-Lim-NPs delayed to(2.61±0.40)h,t1/2 was increased to(6.73±1.54)h,Cmax and AUC0-t,AUC0-∞ were increased to 4.01-fold and 5.65,5.89-fold,respectively.Conclusion Mal-Lim-NPs changed the pharmacokinetic behavior of limonin in vivo and significantly increased the oral absorption,which laid foundation for the following research.
limoninnanoparticlesmaleimide-modifiedBox-Behnken response surface design methodrelease in vitrooral pharmacokinetics
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