Ulcerative colitis (UC) is a chronic and non-specific inflammatory bowel disease that poses a serious threat to individuals' health and lives. Notoginsenoside R1 (R1) alleviates various symptoms caused by UC effectively. However, the application of R1 is somewhat restricted due to its low bioavailability and nontargeted delivery in vivo. Consequently, it is imperative to develop novel strategies to overcome the aforementioned limitations and enhance the efficacy of this drug. To enhance R1's efficacy and targeting ability, polyethylene glycol poly (lactic-co-glycolic acid) nanoparticles loaded with R1 (R1@PEG–PLGA NPs) modified by transferrin (Tf) were prepared in this study and named R1@Tf–PEG–PLGA NPs. R1@PEG–PLGA NPs and R1@Tf–PEG–PLGA NPs were prepared through nanoprecipitation, and the characterization methods were as follows: First, the surface morphology of the NPs was studied through transmission electron microscopy. Second, particle size, polydispersity index (PDI), and zeta potential were measured with a Malvern particle size analyzer, and the Tf grafting rate on the surface of the NPs was determined by using a bicinchoninic acid protein quantification kit. Third, high-performance liquid chromatography was used in determining the drug load (DL), entrapment efficiency (EE), and in vitro release of the prepared preparation. In addition, the fluorescence intensities of fluorescent-labeled NPs absorbed and ingested in Caco-2 cells were observed through in vitro experiments using fluorescence microscopy; the effects of incubation time, incubation temperature, and endocytosis inhibitors on the uptake of nanoparticles were compared; and the uptake-transport mechanism was explored. Finally, in vivo experiments were performed using the oxazolone (OXZ)-induced UC model in Sprague–Dawley (SD) rats to assess the pharmacodynamic effects and tissue distribution of the prepared NPs. The experimentally prepared R1@Tf–PEG–PLGA NPs were round particles with particle size and PDI of 153.50 ± 2.01 and 0.11 ± 0.01, respectively. In addition, the DL of R1@Tf-PEG-PLGA NPs was 24.26

In this work, self-double-emulsifying drug delivery system enteric-coated capsules (PNS-SDE-ECC) were used to enhance the oral bioavailability and anti-inflammatory effects of Panax notoginseng saponins (PNS), which are rapidly biodegradable, poorly membrane permeable, and highly water-soluble compounds. The PNS-SDEDDS formulated by a modified two-step method spontaneously emulsified to W/O/W double emulsions in the outer aqueous solution, which significantly promoted the absorption of PNS in the intestinal tract. The release study revealed that PNS-SDE-ECC exhibited sustained release of PNS within 24 h and the stability study indicated that PNS-SDE-ECC were stable at room temperature for up to 3 months. Furthermore, compared to PNS gastric capsules, the relative bioavailability of NGR1, GRg1, GRe, GRb1, and GRd in PNS-SDE-ECC was increased by 4.83, 10.78, 9.25, 3.58, and 4.63 times, respectively. More importantly, PNS-SDE-ECC significantly reduced OXZ-induced inflammatory damage in the colon by regulating the expression of TNF-α, IL-4, IL-13, and MPO cytokines. Overall, the prepared PNS-SDE-ECC may serve as a viable vehicle for increasing the oral bioavailability of PNS and its anti-inflammatory action on ulcerative colitis.

Notoginsenoside R1 (R1), which originated from the rhizomes and roots of Panax notoginseng, is classified as a Biopharmaceutical Classification System class III drug with good solubility but poor oral absorption. Although R1 can alleviate the inflammation of dextran sulfate sodium (DSS)induced colitis in mice, the problem of acid degradation and low bioavailability limit its application. The purpose of this study was aimed to design one kind of pH-dependent solid dispersion for oral colon-targeted delivery of R1. Using Eudragit S100 (ES 100) and PEG 4000 as the pHdependent carriers, R1 solid dispersion (R1-SD) was fabricated by solvent evaporation method. Scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction analysis indicated that R1-SD was completely formed, the surface was smooth surface and the strip crystal structure of R1 disappeared. The in vitro release profile of R1-SD (R1-ES 100-PEG 4000, 1:7:1, weight ratio) exhibited that R1-SD was not released in media simulating the gastric condition (pH 1.2), but better release characteristics of the drug could be obtained in media simulating the intestinal condition (less than 30% in pH 6.8 phosphate-buffered saline and more than 90% in pH 7.6 condition). The in vitro colon absorption test showed that the absorption rate and cumulative release of R1-SD were higher than those of R1. R1-SD and R1 had apparent protective effect on colon shortening, inflammatory infiltrating tissue injury, weight loss, diarrhea, blood stool in mice with ulcerative colitis induced by DSS, and the protective effect of R1-SD was better than that of R1, which indicated R1-SD has good practical application prospects.

目的 建立鲜百合质量控制方法.方法 采用TLC法对鲜百合进行定性鉴别,HPLC法测定王百合苷B含量;参照2015年版《中国药典》方法,测定水分、总灰分和浸出物含量.结果 TLC定性鉴别采用硅胶G板,以石油醚-二氯甲烷-乙酸乙酯-甲醇(7∶10∶7∶2)为展开系统,10％硫酸乙醇显色,365 nm下检视:鲜百合样品与对照药材在相同位置呈现相同颜色斑点,斑点清晰,重复性好;HPLC含量测定采用Agilent C18色谱柱(4.6 mm×250 mm,5 μm),在流动相乙腈-0.1％磷酸(17 ∶83)、检测波长312 nm、柱温25℃、流速1.0 mL/min、进样量20 μL条件下,王百合苷B在10.27～164.32 mg/L范围内线性关系良好(R2 = 0.999 7),平均加样回收率为100.08％(RSD为2.31％).20批样品中,王百合苷B含量0.62～4.71 mg/g;鲜百合粉末水分、总灰分和水溶性浸出物范围分别为7.53％～10.22％、2.63％～4.88％和23.07％～43.01％.结论 本研究建立的鲜百合质量控制方法准确稳定,重复性好,可用于鲜百合的质量控制.

目的:采用单因素试验与正交试验优化转铁蛋白(Tf)修饰的负载三七皂苷R1的PEG-PLGA纳米粒(R1@Tf-PEG-PLGA NPs)的制备工艺,并对其质量进行评价.方法:采用纳米沉淀法制备负载三七皂苷R1的PEG-PLGA纳米粒(R1@PEG-PLGA NPs),通过单因素试验与正交试验优选其最佳制备条件.将Tf共价偶联在纳米粒表面,制得R1@Tf-PEG-PLGA NPs.以Tf接枝率为指标,通过单因素试验优选其制备条件.采用激光粒度仪和透射电子显微镜对纳米粒进行形态表征及理化参数测定.采用透析法进行纳米粒体外释药研究,并对释药过程进行动力学模型拟合.结果:制得的R1@Tf-PEG-PLGA NPs形态圆整、分散性良好,粒径(153.50±2.01)nm,多分散指数0.11±0.01,Zeta 电位(-17.57±1.45)mV,包封率(50.32±0.86)％,载药量(24.26±0.18)％,蛋白接枝率(42.09±0.62)％.药物24 h累积释放率＞80％,体外释放过程符合Riger-Peppas动力学模型.结论:制得的R1@Tf-PEG-PLGA NPs粒径均一,包封率与载药量适宜,能够延缓药物的释放.

目的 建立超高效液相色谱-串联质谱(UPLC-MS/MS)法同时测定大鼠口服三七总皂苷后血浆中三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb 1、人参皂苷Rd的含量.方法 以柴胡皂苷A为内标,蛋白沉淀法对血浆样品进行处理.色谱柱:ACQUITY BEH C18柱(100 mm×2.1 mm,1.7μm),流动相:乙腈-0.1％甲酸水溶液,梯度洗脱,流速:0.4 mL·min-1.采用电喷雾离子源,负离子模式及多反应监测模式.考察该方法的专属性、标准曲线与定量下限、精密度、提取回收率、基质效应和稳定性.结果 UPLC-MS/MS法检测三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、人参皂苷Rd的标准曲线线性范围分别是2.01～1005.50,1.94～964.80,1.94～969.50,1.85～926.60,1.93～965.20 ng·mL-1,批内与批间精密度分别为0.96％～7.59％、0.77％～7.16％,提取回收率为85.01％～101.99％;基质效应为92.48％～105.81％;在设定的各种条件下稳定性良好.结论 建立的UPLC-MS/MS分析方法简便、快捷,适用于大鼠血浆中三七皂苷R1、人参皂苷Rg1、人参皂苷Re、人参皂苷Rb1、人参皂苷Rd的含量测定.

目的 三七皂苷R1属于生物药剂学分类系统的第Ⅲ类,具有高水溶性低渗透性的特点,口服生物利用度较低.为改善其肠吸收特性,本实验将其制备成磷脂复合物,优化制备工艺并对其质量进行评价.方法 采用溶剂挥发法制备磷脂复合物,以药脂复合率为考察指标,通过单因素实验,对溶剂、药脂比等工艺条件进行优化,并采用扫描电镜、X-射线衍射和差示量热扫描进行表征.同时对其油水分配系数、离体肠吸收率和稳定性进行考察.结果 在四氢呋喃为溶剂,三七皂苷R1-卵磷脂(摩尔比)1∶2,药物质量浓度10 mg·mL-1,温度40℃,2h条件下,三七皂苷R1磷脂复合物复合率可达99.00％;扫描电镜、X-射线衍射和差示量热扫描均验证了三七皂苷R1磷脂复合物的形成.油水分配系数较原料药提高到3.6(水中)和4.1(pH6.8缓冲液中)倍;离体结肠的累积吸收量比原料药显著性增加(P ＜0.001);高温高湿条件下较稳定,但遇强光不稳定,避光条件下室温放置3个月稳定性较好.结论 三七皂苷R1磷脂复合物制备工艺简单可行,复合率高,肠吸收显著提高,稳定性较好,应避光储存,适于工业化生产.