Study On The Saponins PD-Loaded Eudragit Nanoparticles

Objective In this study, Saponins PD-loaded pH-sensitive nanoparticles(SPD-S100-NPs、SPD-L100-NPs、SPD-L100-55-NPs) were prepared. To study thecorrelation of the nanoparticles in vitro, the antitumor activity of its in vitro and in vivo,and investigate its properities and abosorption characters in rat intestine in vivo and invitro, In order to obtain a novel enteric coated nanoparticles.Methods:(1) The SPD-S100-NPs、SPD-L100-Nps and SPD-L100-55-NPs wereprepared by modified quasi-emulsion solvent diffusion technique. Taking particle size,entrapment efficiency and polydisperse index(P.I.) as comprehensive indexes, theorthogonal test design was used to optimize the preparation process.(2) Thecharacteristics of nanoparticles were determined by FT-IR, X-ray diffraction, DSC, etc.;in vitro drug release of nanoparticles colloid and lyophilized powder were alsoinvestigated.(3) In vitro anti-tumor activity of the three nanoparticles were studied ascell apoptosis and cytotoxicity on human hepatoma cell lines SMMC-7721, HepG2andBel-7402by flow cytometry and MTT Assay respectively.(4) In vivo anti-tumoractivity of the nanoparticles was studied as tumor inhibitory activity in mice bearingH22hepatoblastoma tumor, including neoplasm volume, inhibition on body weight,inhibition rate on tumor weight, immune organ coefficient; Pathology characteristic ofstripped tumor was observed by biological microscope.(5) The absorption character andregularity were studied at various intestine segments and at different concentration.Results：(1) The three kinds of nanoparticles of average particle size were(71.8±0.9) nm、(65.2±1.6) nm、(65.1±3.3) nm, the entrapment efficiency were(99.38±0.09)%、(99.13±0.20)%、(98.97±0.20)%and the polydisperse index were0.226±0.006、0.384±0.008、0.196±0.002, respectively.(2) The nanopanicles had smallsize，were look aroulld or e11ipse and regular under TEM. In FT-IR、DSC and X-raydiffraction graphs, the diagnostic absorption peak of Fd-SPD-NPs were significantly different from the physical mixture. In vitro SPD release of nanoparticles had pHsensitivity characteristic, and drug release followed Higuchi equation.(3) Comparisonwith SPD, the results of SPD-L100-55-NPs displayed the highest inhibition level, nextis SPD-S100-NPs.(4) The antitumor activity suggested that tumor growth waseffectively inhibited to all treatment groups with SPD-L100-55-NPs being the mosteffective, followed by SPD-S100-NPs and the next was SPD.(5) The intestinalabsorption of SPD with passive diffusion mechanism, the absorption rate constants (Kα)of SPD in different segments were jejunum>duodenum>colon>ileum． Theconcentration had no distinctive effect on the absorption kinetics，which suggested drugabsorption is not dose-dependent．It was found that the Kαof SPD-L100-55-NPs waslower than SPD solution，and t1/2was extension．Conclusions: Optimized preparation technique of NPs was satisfied with thesimple process, low cost, and stable reproducibility. The pH sensitivity and sustaineddrug release characteristic of NPs were showed in vitro, hepatocyte-targeting andanti-tumor activity of SPD was improved both in vitro and in vivo. The intestinalabsorption models in vivo was established．The intestinal absorption mechanisms ofSPD solution and NPs were investigated．It is showed that NPs significantly enhanceddrug absorption, compared with SPD solution．Intestinal absorption kinetics providedmethods for profound study on the process in vivo and new oral drug development．Thisnovel enteric coated nanoparticles had wide perspective and practicability on theclinical of SPD.