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Mixed nanomicelles loaded with thymopeptides-sodium deoxycholate/phospholipid improve drug absorption

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Chinese Journal of Natural Medicines 2014年第1期12卷 65-70页

作者： JIN Shi-Xiao JIN Shi-Ying LV Qing-Yuan FU Shan-Shan HAN Jin YUAN Hai-Long Department of Pharmacy 302 Military Hospital School of pharmaceutics Chengdu University of TCM

AIM: To improve the absorption of thymopeptides(TH) by preparing sodium deoxycholate/phospholipid-mixed nanomicelles(SDC/PL-MMs). METHODS: TH-SDC/PL-MMs were prepared by a film dispersion method, and then evaluated using photon correlation spectroscopy(PCS), zeta potential measurement, as well as their physical stability after storage for several days. Furthermore, in situ intestinal single-pass perfusion experiments and pharmacodynamics in immunodeficient mice were performed to make a comparison with TH powders and the control drug in absorption properties. RESULTS: A narrow size distribution of nanomicelles, with a mean particle size of(149 ± 8.32) nm and a zeta potential of(-31.05 ± 2.52) mV, was obtained. The in situ intestine perfusion experiments demonstrated a significant advantage in absorption characteristics for TH compared to the other formulations, and oral administration of TH-SDC/PL-MMs potentiated an equivalent effect with i.h. TH in pharmacodynamic studies in immunodeficient mice. CONCLUSIONS: TH-SDC/PL-MMs prepared by a film dispersion method are able to improve the absorption of TH. SDC/PL-MMs might be a good approach for the more effective delivery of drugs like TH.

关键词： In situ intestinal absorption sodium deoxycholate Phospholipid Micelles Thymopeptides Immunodeficiency

Tunable Separation of Single-Walled Carbon Nanotubes by Dual-Surfactant Density Gradient Ultracentrifugation

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Nano Research 2011年第7期4卷 623-634页

作者： Pei Zhao Erik Einarsson Georgia Lagoudas Junichiro Shiomi Shohei Chiashi Shigeo Maruyama Department of Mechanical Engineering The University of Tokyo Tokyo 113-8656 Japan Global Center of Excellence for Mechanical Systems Innovation The University of Tokyo Tokyo 113-8656 Japan Department of Bioengineering Rice University Houston TX 77005 USA

We present a systematic study of the effects of surfactants in the separation of single-walled carbon nanotubes （SWNTs） by density gradient ultracentrifugation （DGU）. Through analysis of the buoyant densities, layer positions, and optical absorbance spectra of SWNT separations using the bile salt sodium deoxycholate （DOC） and the anionic salt sodium dodecyl sulfate （SDS）, we clarify the roles and interactions of these two surfactants in yielding different DGU outcomes. The separation mechanism described here can also help in designing new DGU experiments by qualitatively predicting outcomes of different starting recipes, improving the efficacy of DGU and simplifying post-DGU fractionation.

关键词： Single-walled carbon nanotubes density gradient ultracentrifugation sodium deoxycholate sodium dodecyl sulfate

Oxidative stress, antioxidants and intestinal calcium absorption

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World Journal of Gastroenterology 2017年第16期23卷 2841-2853页

作者： Gabriela Diaz de Barboza Solange Guizzardi Luciana Moine Nori Tolosa de Talamoni Laboratorio“Dr.Fernando Canas” Cátedra de Bioquímica y Biología MolecularFacultad de Ciencias MédicasINICSA(CONICET-Universidad Nacional de Córdoba)Pabellón ArgentinaCiudad UniversitariaCórdoba 5000Argentina

The disequilibrium between the production of reactive oxygen(ROS) and nitrogen(RNS) species and their elimination by protective mechanisms leads to oxidative stress. Mitochondria are the main source of ROS as by-products of electron transport chain. Most of the time the intestine responds adequately against the oxidative stress, but with aging or under conditions that exacerbate the ROS and/or RNS production, the defenses are not enough and contribute to developing intestinal pathologies. The endogenous antioxidant defense system in gut includes glutathione(GSH) and GSH-dependent enzymes as major components. When the ROS and/or RNS production is exacerbated, oxidative stress occurs and the intestinal Ca2+ absorption is inhibited. GSH depleting drugs such as DLbuthionine-S,R-sulfoximine, menadione and sodium deoxycholate inhibit the Ca2+ transport from lumen to blood by alteration in the protein expression and/or activity of molecules involved in the Ca2+ transcellular and paracellular pathways through mechanisms of oxidative stress, apoptosis and/or autophagy. Quercetin, melatonin, lithocholic and ursodeoxycholic acids block the effect of those drugs in experimental animals by their antioxidant, anti-apoptotic and/or anti-autophagic properties. Therefore, they may become drugs of choice for treatment of deteriorated intestinal Ca2+ absorption under oxidant conditions such as aging, diabetes, gut inflammation and other intestinal disorders.

关键词： Transcellular and paracellular Ca2+pathways DL-buthionine-S R-sulfoximine Menadione sodium deoxycholate Lithocholic acid Ursodeoxycholic acid Melatonin

Glutathione depleting drugs, antioxidants and intestinal calcium absorption

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World Journal of Gastroenterology 2018年第44期24卷 4979-4988页

作者： Luciana Moine María Rivoira Gabriela Díaz de Barboza Adriana Pérez Nori Tolosa de Talamoni Laboratorio "Dr. Fernando Canas" Cátedra de Bioquímica y Biología Molecular Facultad de Ciencias Médicas INICSA (CONICET-Universidad Nacional de Córdoba) Córdoba 5000 Argentina

Glutathione （GSH） is a tripeptide that constitutes one of the main intracellular reducing compounds. The normal content of GSH in the intestine is essential to optimize the intestinal Ca2＋ absorption. The use of GSH depleting drugs such as DL-buthionine-S,R-sulfoximine, menadione or vitamin K3, sodium deoxycholate or diets enriched in fructose, which induce several features of the metabolic syndrome, produce inhibition of the intestinal Ca2＋ ab-sorption. The GSH depleting drugs switch the redox state towards an oxidant condition provoking oxida-tive/nitrosative stress and inflammation, which lead to apoptosis and/or autophagy of the enterocytes. Either the transcellular Ca transport or the paracellular Ca route are altered by GSH depleting drugs. The gene and/or protein expression of transporters involved in the transcellular Ca2＋ pathway are decreased. The favonoids quercetin and naringin highly abrogate the inhibition of intestinal Ca2＋ absorption, not only by restoration of the GSH levels in the intestine but also by their anti-apoptotic properties. Ursodeoxycholic acid, melatonin and glutamine also block the inhibition of Ca2＋ transport caused by GSH depleting drugs. The use of any of these antioxidants to ameliorate the intestinal Ca2＋ absorption under oxidant conditions associated with different pathologies in humans requires more investigation with regards to the safety,pharmacokinetics and pharmacodynamics of them.

关键词： Glutathione Transcellular and paracellular Ca^2+pathways DL-buthionine-S,R-sulfoximine Fructose rich diet Menadione sodium deoxycholate Glutamine Ursodeoxycholic acid Melatonin Quercetin Naringin

The separation single-wall carbon nanotubes on length by sepharose gel

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Science China(Physics,Mechanics & Astronomy) 2012年第7期55卷 1178-1182页

作者： REN LingLing ZHAO MingYuan WANG ZhiHua National Institute ofMetrology Beijing 100013 China Department of Applied Chemistry Beijing University of Chemical Technology Beijing 100013 China

The separations of single-wall carbon nanotubes on length by sepharose gel were investigated in this work. The solutions of sodium dodecyl sulfate and sodium deoxycholate were applied as the eluent in sequence. SEM and Raman were used to characterize the length of nanotube bundles. The results show that the longer nanotubes were eluted out first, and then the shorter tubes were followed by the sodium dodecyl sulfate. However, the separated order was totally reversed by the sodium deoxycholate. By this method, the process generated nanotube fractions not only were narrower in length distributions, but also could control the separation orders by changing the eluents. Moreover, the separation principle was also discussed.

关键词： single-wall carbon nanotubes length separation sepharose gel sodium dodecyl sulfate sodium deoxycholate

猪胆汁提取物及去氧胆酸钠对人阴道毛滴虫作用的电镜观察

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西安交通大学学报(医学版) 1986年第2期 126-128页

作者：郭仁舆邱曙东西安医科大学组织胚胎学教研室

本研究在超微结构水平上证明了猪胆汁提取物及其有效成份去氧胆酸钠对培养的人阴道毛滴虫具有碎解作用,鞭毛及尾突断离,质膜及内膜系统如吞噬小体和氢化小体的界膜、核膜等破损,细胞质凝集,乃至整个虫体完全碎解。其作用机制可能与药物... 详细信息

本研究在超微结构水平上证明了猪胆汁提取物及其有效成份去氧胆酸钠对培养的人阴道毛滴虫具有碎解作用,鞭毛及尾突断离,质膜及内膜系统如吞噬小体和氢化小体的界膜、核膜等破损,细胞质凝集,乃至整个虫体完全碎解。其作用机制可能与药物的表面活性作用促进了滴虫生物膜系统结构脂类的降解直接有关。

关键词： pig bile sodium deoxycholate trichomonas vaginalis ultrastructure

Transport and uptake characteristics of a new derivative of berberine(CPU-86017) by human intestinal epithelial cell line: Caco-2

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Acta Pharmacologica Sinica 2003年第12期24卷 11-17页

作者： YANG Hai-Tao, WANG Guang-Ji Center of Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China Center of Pharmacokinetics China Pharmaceutical University Nanjing 210009 China

AIM: The characteristics of transepithelial transport and uptake of CPU-86017 {[7-(4-chlorbenzyl)-7,8,13,13α-tetrahydroberberine chloride, CTHB]}, a new antiarrhythmia agent and a new derivative of berberine, were investigated on epithelial cell line (Caco-2) to further understand the absorption mechanism of berberine and its derivatives. METHODS: Caco-2 cell was used. RESULTS: 1) The permeability coefficient from the apical (AP) to basolateral (BL) of CPU-86017 was approximately 5 times higher than that from BL-to-AP transport. The effects of a P-glycoprotein (P-gp) inhibitor-cyclosporin A, some surfactants, and lower pH on the transepithelial transport of CPU-86017 were also observed. Cyclosporine A at 7.5 mg/L had no effect on the transepithelial electrical resistance (TEER); an about 4-fold enhancement on the transepithlial transport of CPU-86017 was observed. Some surfactants (sodium citrate, sodium deoxycholate, and sodium dodecyl sulfate) at 100 μmol/L and low pH (pH=6.0) induced a reversible d

关键词： CPU-86017 berberine Caco-2 cell cyclosporine A sodium dodecyl sulfate sodium citrate sodium deoxycholate

Effect of Enzymes in Buccal Mucous Membrane on Buccal Absorption of Insulin

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Journal of Chinese Pharmaceutical Sciences 2002年第1期11卷 28-33页

作者：杨天智陈大兵陈启龙张强北京大学药学院药剂教研室北京100083

To evaluate the effect of proteolytic enzymes on the absorption of insulin in the buccal mucosa, the trichloroacetic acid (TCA) method was used to estimate the degradation of insulin under different conditions in the buccal mucosal homogenates. In vivo experiments estimating the enhancement of hypoglycaemic effect by enzyme inhibitors were also conducted. The results showed that proteolytic enzymes in the buccal mucosa were less active than in the intestine. Bacitracin, aprotinin and sodium deoxycholate could inhibit the degradation of insulin in the buccal mucosal homogenates. The degradation of insulin in buccal mucosal homogenates of normal hamsters was smaller than that of diabetic hamsters. In vivo experiments of hypoglycaemia supported the in vitro results. When given buccally, bacitracin, aprotinin and sodium deoxycholate could increase the relative pharmacological bioavailability of insulin. When co-administered with aprotinin(0.1%), bacitracin(0.5%) and sodium deoxycholate(5%), the relative pharmacological bioavailabilities of insulin were 4.84%, 6.60% and 14.95% respectively. The in vitro and in vivo results suggest that proteolytic enzymes are present in the buccal mucosa, which limit absorption of insulin. Co-administration with some enzyme inhibitors can improve the bioavailability of insulin via buccal delivery and sodium deoxycholte is more efficient than some enzyme inhibitors used for improving buccal absorption.

关键词： Insulin Buccal mucosa Trichloroacetic acid (TCA) method Bacitracin aprotinin sodium deoxycholate Relative pharmacological bioavailability