The aim of this studywas to investigate the effect of two novel self-microemulsifying drug delivery systems (SMEDDS) containing Labrasol with different dilutions on tight junctions. Changes in barrier properties of Caco-2 cell monolayers, including transepithelial electrical resistance (TEER) and permeability to the paracellular marker, i.e., mannitol, were assessed in response to dilutions and surfactants contents within formulations. The cytotoxicity of SMEDDS and the effect of surfactants on Caco-2 cells were evaluated by the MTT. Changes in subcellular localization of the tight junction proteins, ZO-1 and F-actin, were examined by confocal laser scanning microscopy. Results demonstrated that negatively charged SMEDDS with different dilutions had no effect on the TEER, but significantly increased the permeability of mannitol. In contrast, the positively charged formulation showed a dilution-dependent reduction in TEER. A corresponding increase in mannitol permeability of up to 29.4-fold to 64.7-fold greater than the control was also observed across the monolayer. Labrasol with the concentration of 0.1 and 1% was shown to increase the permeability of mannitol by 4.6-fold and 33.8-fold, respectively. The mechanism of opening of tight junctions was found to involve F-actin-related changes and redistribution of ZO-1.

嵌段共聚物胶束作为抗肿瘤药的载体，可降低网状内皮系统对抗肿瘤药物的识别和摄取、减少药物的肾排泄及其在正常组织的积蓄；增加了药物在血中的稳定性和在肿瘤组织的积蓄量，是一种长效、高效、安全的抗肿瘤药物载体。嵌段共聚物胶束在肿瘤治疗中的应用具有广阔的发展前景，为肿瘤治疗带来了新的曙光。

Aim: To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123. Methods: The polymeric micelles of paclitaxel with Pluronic P123 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control. Results: Using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic P123 micelles in release medium containing 1mol/L sodium salicylate for 24 h at 37℃. In the pharmacokinetic assessment, t1/2β and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study. Conclusion: Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.

目的 探明萘普生钠在肠道各区段的吸收动力学特征、吸收部位及吸收机制，以期对药物的长效缓释制剂的设计提供重要的依据。方法 采用大鼠在体肠灌流吸收实验，研究了萘普生钠的吸收部位和吸收动力学特征。结果 萘普生钠在小肠部位吸收良好，吸收速度按空肠、回肠、十二指肠、结肠的顺序依次下降，吸收速度常数依次为0.596、0.536、0.378、0.146h-1。药物在肠道的吸收呈现一级吸收动力学特征且吸收机制为被动吸收。药物的吸收窗为结肠以上部位。结论 萘普生钠的吸收窗比较长，适于制备日服一次的缓释给药系统。而结肠的吸收速度常数大约是小肠段的3P10，这又提示设计萘普生钠日服一次的缓释制剂时，最好能延长制剂在胃肠道上中部的滞留时间。

Panax notoginseng is used as a therapeutic agent to stop haemorrhages and a tonic to promote health in Chinese medicine. Currently saponins of P. notoginseng (PNS) are especially given attentions for their hemorheological properties. The pharmacokinetic profiles of the main PNS are still not accurately investigated. Therefore, our preliminary aim is to elucidate the pharmacokinetic features of ginsenoside Rb1 (Rb1) and ginsenoside Rg1 (Rg1), two of the main PNS in rats. Firstly, quantitive analysis of Rb1 and Rg1 in saponins of P. notoginseng was studied and the most suitable assay method by HPLC for blood sample were established. Then Rb1 and Rg1 in the same serum were determined after administering PNS to rats. The decline of Rb1 in serum could be described by a two-compartment model. The half-life of a phase was 23.40min and that of b phase was 17.96 h. Rb1 was absorbed from the digestive tract and the bioavailability via P.O. was 4.35%. The pharmacokinetics of Rg1 in rats also could be described by a two-compartment model. The half-lives of Rg1 were 24.23min for a phase and 14.13h for b phase. Rg1 could be absorbed in the digestive tract and the oral bioavailability was 18.40%. Both of the low oral bioavailability of Rb1 and rapid reduction of Rg1 in blood indicated that formula modification is necessary.

目的 研究三七总皂苷鼻腔用粉雾剂以混悬液形式给药后在大鼠体内的药代动力学过程及对心脑血管疾病的保护作用。方法 HPLC测定三七总皂苷混悬液大鼠鼻腔给药后血样中人参皂苷Rg1的浓度，考察药物在体内的动力学过程，并计算其绝对生物利用度；结扎SD大鼠的左冠状动脉建立急性缺血性心肌梗死模型，夹闭沙鼠的双侧颈总动脉建立脑缺血再灌注模型，考察三七总皂苷混悬液对心脑血管疾病的保护作用。结果 三七总皂苷混悬液鼻腔给药后，Rg1在大鼠体内的过程符合二室模型，其绝对生物利用度为103156%；对大鼠急性缺血性心肌梗死及沙鼠脑缺血再灌注所引起的脑水肿和脑卒中症状均具有明显的缓解作用，且呈剂量依赖性，剂量越高，保护作用越强。结论 药代动力学和药效学结果证明，三七总皂苷鼻腔给药制剂具有很好的开发前景。

目的：确定三七总皂苷鼻腔用粉雾剂的较优处方。方法：以人参皂苷Rb11h、12h和人参皂苷Rg11h、12h的累积释放度、制剂的生物粘附强度及蟾蜍上腭黏膜纤毛毒性为指标，采用星点设计2效应面优化法，确定较优处方。结果：当三七总皂苷、微晶纤维素和中等粘度羟丙基纤维素的比例分别为31、60和9时，Rb11h、12h和Rg11h、12h的累积释放度分别为6.82、53.25和83.47、95.09，生物粘附强度为78min，蟾蜍上腭黏膜纤毛持续运动时间为为生理盐水组的94.84，几乎没有纤毛毒性。结论：应用星点设计2效应面优化法能够快速方便地得到三七总皂苷鼻腔用粉雾剂的较优处方。

以Maisine 35-1为油相，Cremophor EL、Labrasol为表面活性剂，Transcutol P为助表面活性剂，制得9-硝基 喜树碱（1）负电荷自微乳化制剂；在此基础上加入油胺作为正电荷剂可得1正电荷自微乳化制剂。用HPLC法测定大鼠体内1含量。结果表明含药的负、正电荷自微乳化制剂经水稀释10倍时，粒径分别为（24.7±7.9）和（25.0±8.3）nm，z电位分别为-（4.8±0.5）和（2.4±0.9）mV。大鼠分别以6mg/kg的剂量灌胃给予1溶液和负、正电荷自微乳化制剂后，三者的Cmax分别为（93.8±72.8）、（176.4±93.4）和（128.9±49.1）ng/ml；AUC分别为（127.6±51.6）、（331.9±261.1）和（595.1±42.0）ng·ml-1·h；MRT 分别为（1.6±0.9）、（1.2±0.6）和（4.3±2.4）h。 正、负电荷自微乳化制剂的相对生物利用度分别是溶液的4.7和2.6倍，表明前者提高药物的口服吸收作用优于后者（P<0.05）。

目的 研究能够提高三七总皂苷生物利用度的给药途径和制剂。方法 采用鼻腔给药筛选提高药物生物利用度的适宜制剂。结果 本试验中制备的制剂在不引起黏膜刺激性的条件下，大幅度提高了PNS的生物利用度。结论 可从给药途径和剂型两方面考虑提高药物吸收，降低刺激性。

目的 制备三七总皂苷（P anax notog inseng saponins, PN S）脂质体，研究其药剂学性质及在大鼠体内药动学行为。方法 采用薄膜分散法制备PNS脂质体，考察其形态、粒径、包封率及稳定性，采用肺部滴注给药考察脂质体在大鼠体内的药动学行为。结果 PNS脂质体包封率为78150%，平均粒径为115Lm，外形圆整，体外泄漏慢，需低温保存。PNS脂质体经大鼠肺部滴注给药后，体内人参皂苷Rb1的药动学参数分别为T1ö2A=7100h，T1ö2B=27172h,AUC=221819Lg·hömL，绝对生物利用度为70114%。结论 PNS脂质体包封率高，性质稳定，延长PNS在血循环的时间，提高了经血管外给药途径的PNS生物利用度。