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Objective To obtain the intestines absorption of TPGS-CS/PTX polymeric micelles in rats, a drug-loaded micelle system was established by a kind of amphiphilic copolymer, D-α-tocopherol polyethylene glycol 1000 succinate-chitosan (TPGS-CS) was prepared by grafting D-α-tocopherol polyethyleneglycol 1000 succinate (TPGS) as the donor of the micelle hydrophobic group on chitosan (CS) as bioadhesive material, and loading paclitaxel as model drug. Methods TPGS was activated by its hydroxy-terminal carboxylation with succinic anhydride (SA) and 4-dimethylaminopyridine (DMAP). The TPGS-CS copolymer was prepared by the amidation of free amino groups on CS. The chemical structure of the TPGS-CS grafted copolymer was characterized by Fourier transform-infrared spectroscopy (FT-IR) and Nuclear magnetic resonance spectroscopy (NMR). The polymer micelle loading paclitaxel was selected as model drug and TPGS-CS/PTX was prepared by ultrasonic emulsification method. The encapsulation efficacy (EE) and drug loading (DL) were determined by high performance liquid chromatography (HPLC). The particle size, Zeta potential, and size distribution of the micelle system were measured by dynamic light scattering (DLS). The surface morphology of the micelles was investigated by Transmission electron microscopy (TEM). The in vivo intestines absorption rate (Ka) of paclitaxel-loaded TPGS-CS micelle was calculated in rats. Results The results of FT-IR and 1H NMR indicated that the copolymer (TPGS-CS) was synthesized. The TEM result showed that the formed particles were uniform in shape without aggregation. The Ka of TPGS-CS/PTX was 20 percent higher in comparison to the reference preparation, it indicated that this polymeric micelles could increase bioavailability. Conclusion The proposed TPGS-CS copolymer was successfully synthesized in this experiment, and the drug-loaded micelles prepared by ultrasonic emulsification exhibited good characteristics compared with the reference preparation, the Ka of paclitaxel was increased to some extent to promote oral absorption of the drug.
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OBJECTIVE: To prepare small interfering RNA(siRNA) lipid complexes (TPOS-L/siRNA) modified by D-α-tocopheryl poly (2-ethyl-2-oxazoline) succinate (TPOS). METHODS: The conventional siRNA lipid complexes (CLs /siRNA) and PEGylated CLs /siRNA (PEG-L/siRNA) were used as controls. CLs /siRNA was prepared by mixing blank CLs and siRNA directly of equal volume according to the electrostatic interaction of positive and negative charges. The encapsulation efficiency, morphology, stability, in vitro release and cell uptake of TPOS-L/siRNA were investigated. RESULTS: The CLs/siRNA had obvious lipid bilayer structure, the encapsulation efficiency (EE) was (86.68 ± 1.41)%, and the particle size of CLs /siRNA was less than 200 nm. The modification with TPOS or PEG-DSPE had no significant effect on the EE and particle size of CLs /siRNA, which could endow the lipid complexes with good stability. In addtion, TPOS-L/siRNA had good pH-sensitive property, and could respond to slightly acidic environment, which significantly enhanced the cell uptake. CONCLUSION: TPOS can construct good siRNA carrier and increase the stability and pH sensitivity of the nanocarrier.
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AIM To prepare D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-modified artesunate liposomes and to investigate the in vitro anti-tumor activity.METHODS The liposomes prepared by thin-film dispersion method were characterized by transmission electron microscopy and particle size analyzer,and the encapsulation efficiency was determined by ultrafiltration centrifugation.The liposomes' cytotoxicity to human hepatoma HepG2 cells was evaluated by MTT method.RESULTS The average particle size,PDI,Zeta potential,encapsulation efficiency,drug loading of the liposomes were 126.7 nm,0.182,-10.1 mV,78.8％ and 18.38％,respectively.The liposomes displayed a significant inhibition on HepG2 cells with the IC50 value of 0.034 μmol/mL.CONCLUSION Compared with non-TPGS-modified artesunate liposomes,the TPGS-modified artesunate liposomes prepared by this method afford smaller vesicle size,better stability and higher encapsulation efficiency with stronger in vitro anti-tumor activity.
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Objective: To prepare GEN-VES-TPGS nano-micelles and improve the oral bioavailability of genistein (GEN). Methods: GEN-VES-TPGS nano-micelles, made by film hydration, were evaluated with particle size, entrapment efficiency, and drug-loading as indexes. Single factor experiment was used to optimize the formulation and productive technology, including dosages of TPGS, VES, GEN, hydration volume, temperature, and time. Morphology of nano-micelles, release rate in vitro, and pharmacokinetics in rat were investigated. Results: The results showed GEN-VES-TPGS nano-micelles presented with good clarity, appropriate particle diameter (43.50 ± 1.65) nm, negative charge, when the dosages of TPGS, VES, GEN were 200, 30, and 6 mg, respectively. Meanwhile, a condition of 15 mL, 50 ℃ at 3 h to hydrate was necessary to prepare. In this setting, the encapsulation efficiency of the nano-micelles was (98.99 ± 0.69)% and drug-loading rate was (2.57 ± 0.04)%. The pharmacokinetic results in rats showed the oral bioavailability of GEN-VES-TPGS nano-micelles was 162.96% of the GEN APIs. Conclusion: The prepared GEN-VES-TPGS nano-micelles have small particle size and good stability, and increase the oral bioavailability of GEN evidently.
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Objective: To study the chemical constituents from the leaves of Adinandra nitida. Methods: The chemical constituents of the plant were isolated and purified by column chromatography and their structures were elucidated on the basis of physicochemical properties and spectral data. Results: Eleven triterpenoids, two diterpenoids, and two steroids were obtained and determined to be ursolic acid (1), 18-hydroxyursolic acid (2), 2α,3α-dihydroxyursolic acid (3), 3α,19α-dihydroxyursolic acid (4), euscaphic acid (5), 3β,19α,23-trihydroxyursolic acid (6), 2α,3α-dihydroxyursolic acid-28-O-β-D-glucopyranoside (7), kajiichigaside F1 (8), oleanolic acid (9), arjunetin (10), betulinic acid (11), cassipourol (12), α-tocopherol (13), daucosterol (14), and β-sitosterol (15). Conclusion: Compounds 1-4, 6, 7, 9, and 11-13 are obtained from the leaves of A. nitida for the first time.
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Objective: To study the chemical constituents of Pilea sinofasciata. Methods: Column chromatography, such as silica gel, Sephadex LH-20, and preparative HPLC, was used to isolate and purify the compounds. Spectroscopic methods like MS, 1H-NMR, and 13C-NMR, and the physical constants were used to elucidate their structures. Results: Nineteen compounds were isolated from 95% ethanol extracts of P. sinofasciata, including α-tocopherol (1), stigmasterol (2), epihernandulcin (3), hernandulcin (4), benzoic acid (5), ethyl linolenate (6), ethyl hexadecanoate (7), α-amyrin (8), palmitic acid (9), behenic acid (10), adenosine (11), indole-3-carboxylic acid (12), protocatechuate (13), gallic acid (14), betulinic acid (15), oleanolic acid (16), potassium nitrate (17), diosmetin 7-O-β-D-glucopyranoside (18), and 3-O-β-D-xylopyranosyl (1→2)-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl oleanolic acid (19). Conclusion: All of the compounds are isolated from the plant for the first time.
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OBJECTIVES: To assess the absorption of α-tocopherol acetate and 18β-glycyrrhetinic acid, which are used as active ingredients in toothpaste, into a reconstructed gingival tissue. METHODS: EpiGingival™ tissues were treated with a 25% slurry of toothpaste containing 2% α-tocopherol acetate and 0.3% 18β-glycyrrhetinic acid, for 2 minutes. The treatment was repeated up to 6 times, with 1 hour intervals. After completion of all treatments, the active ingredients in the tissue extracts and receiver solutions were measured by high performance liquid chromatography. RESULTS: Although α-tocopherol acetate was not detected, α-tocopherol was detected in the tissue extracts, indicating that α-tocopherol acetate was bioconverted to α-tocopherol after absorption. We could detect 18β-glycyrrhetinic acid both in the tissue extracts and in the receiver solutions, with a positive correlation to the number of treatments. CONCLUSIONS: We found that our toothpaste effectively delivered α-tocopherol acetate and 18β-glycyrrhetinic acid to a reconstructed gingival tissue in vitro.
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Absorção , Cromatografia Líquida , Técnicas In Vitro , Doenças Periodontais , Extratos de Tecidos , Cremes DentaisRESUMO
Objective To analyze peroxide value and anisidine value of ethyl polyenoate soft capsules and imported drugs and evaluate the oxidative stability.Methods The analysis was carried out on a TSK gel ODS-100 V(250 mm ×4.6 mm,5μm)with methanol-water(98:2,V/V)as the mobile phase to determine the structure of the vitamin E as antioxidant.The influence on the antioxidation effect of tocopherol acetate andα-tocopherol as excipient in omega-3 polyunsaturated fatty acid ethyl ester drugs was evaluated.Results The structure of vitamin E as antioxidant in domestic drugs was acetate, while vitamin E as excipient in foreign drugs had the structure of α-tocopherol monomer.As antioxidant, the antioxidation effect of tocopherol acetate was better thanα-tocopherol.The structure of vitamin E had a direct impact on the antioxidation effect of omega-3 polyunsaturated fatty acid ethyl ester drugs.Conclusion The studies provide the basis for evaluate rationality of antioxidant in ethyl polyenoate soft capsules scientifically, which has positive significance for controlling the quality of the drug effectively.
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Objective: To investigate the effect of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) on the inhibition of proliferation of breast cancer cells MCF-7 by baohuoside I. Methods: The cytotoxicity of baohuoside I to MCF-7 cells was determined by MTT assay, the cellular uptake of baohuoside I was detected by fluorescence microscopy, and the intracellular baohuoside I was determined by HPLC. Results: The effect of baohuoside I on the inhibition of MCF-7 cell proliferation was enhanced in the presence of TPGS, especially on lower concentration. The uptake rates of MCF-7 within 2 h were 29.51%, 38.12%, and 40.37%, when the proportions of baohuosaide I and TPGS were 1:1, 1:2, and 1:4, respectively. The ratios were increased by 27.92%, 65.24%, and 74.99% compared with those using baohuoside I only. Conclusion: TPGS can increase the uptake rate of baohuoside I in MCF-7 cells and enhance the inhibition of MCF-7 cell proliferation.
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Objective: To prepare and optimize the prescription of colchicine ethosomes containing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and to investigate its feasibility as a carrier for transdermal drug delivery. Methods: The colchicine ethosomes containing TPGS were prepared by the injection-sonication method. And the encapsulation efficiency (EE) was determined by minicolumn centrifugation method. The prescription of ethosomes was optimized by uniform design with EE as the evaluation index, and the physicochemical properties of the optimized ethosomes were investigated. Characterization of the vesicles was based on particle size, Zeta potential, entrapment efficiency, and transmission electron microscopy (TEM). The transdermal permeation characteristics of ethosomes, colchicine 30% ethanol solution, and colchicine ethosomes containing TPGS were compared by using Franz diffusion cells. Results: The optimized formulation was as follows: The contents of soybean phospholipid and TPGS were 350 and 50 mg, respectively. In addition, the concentration of ethanol was 36.44%. The average EE, particle size, polydispersity index, and Zeta potential were (74.71 ± 2.18)%, (89.6 ± 3.5) nm, 0.201 ± 0.008, and (-34.6 ± 2.7) mV, respectively. The in vitro experiment showed that the transdermal flux, permeation rate, and skin deposition of colchicine ethosomes were (64.49 ± 5.61) μg/cm2, (2.84 ± 0.23) μg/(cm2∙h), (128.22 ± 11.64) μg/cm2, and the transdermal flux, permeation rate, and skin deposition of colchicine ethosomes containing TPGS were (91.36 ± 7.11) μg/cm2, (4.73 ± 0.38) μg/(cm2∙h), and (182.84 ± 14.37) μg/cm2, respectively, which was significantly higher than those in ethosomes. Conclusion: The colchicine ethosomes containing TPGS show high EE and obviously enhance the percutaneous absorption of colchicine, which might be a potential carrier for transdermal drug delivery.
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Objective To explore the protective effect of α-tocopherol succinate (α-TOS) against early hematopoietic injury in mice with acute radiation sickness. Methods Male C57BL/6J mice 6-8 weeks old were randomly divided into normal group, irradiation group and α-TOS group (n=10), 400mg/kg of α-TOS was subcutaneous injected into the mice of α-TOS group 24 hours before irradiation, while vehicle was given to the mice of irradiation group. The 30-day survival rate of mice having received 9.0Gy irradiation, and the mean survival time of non-survivors were recorded. Analysis of peripheral blood was performed in mice receiving 6.5Gy irradiation at days 1, 4, 7, 10, 14, 18, 22, 31 and 45, while the number of bone marrow colony-forming cells (CFCs) and hematopoietic stem/progenitor cells were counted at 2-hour and 24-hour after irradiation. Bone marrow cells collected from 6.5Gy irradiated mice and EGFP transgenic mice were mixed in a ratio of 10:1, and then transplanted into lethal dose-irradiated mice, and the proportion of EGFP positive cells in the peripheral blood was recorded after 35 days. Results α-TOS raised the survival rate and mean survival time of mice suffering from 9.0Gy irradiation, improved the recovery of the peripheral blood picture of mice suffering from 6.5Gy irradiation, and increased the number of bone marrow colony-forming cells and hematopoietic stem/progenitor cells in the mice 24 hours after 6.5Gy irradiation. The competitive transplantation experiments showed that α-TOS markedly diminished the proportion of EGFP positive cells in the peripheral blood in lethal dose-irradiated mice at day 35. Conclusion α-TOS could effectively protect the hematopoietic stem/progenitor cells from radiation injury in γ-ray irradiated mice, promote the recovery of peripheral blood cells, and improve the survival rate.
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OBJECTIVE: To review the applications of D-α-tocopherol polyethylene glycol succinate (TPGS) as a drug carrier in pharmaceutical preparation.
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OBJECTIVE: To study the oral absorption of paclitaxel-loaded mixed micelles made of D-α-tocopherol polyethylene glycol 1000 succinate(TPGS) and sodium cholate(NaC) in rats. METHODS: Paclitaxel-loaded mixed micelles were prepared by film dispersion method. The Zeta potential and diameter distribution of TPGS/NaC mixed micelles were measured using laser size scattering determinator. The morphology of micelles was observed by transmission electron microscope. Dialysis method was used to evaluate the release behavior of drug-loaded micelles in vitro. The absorption kinetics was obtained by in situ perfusion method in rats. RESULTS: Most of the mixed micelles were spherical with an average diameter of 24.2 nm and the Zeta potential was -7.84 mV. Compared to the bulk drug, the apparent absorption rate constant (Ka)of paclitaxel-loaded mixed micelles was increased significantly. CONCLUSION: TPGS/NaC mixed micelles can improve the oral absorption of paclitaxel and increase its oral bioavailability.
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Objective To investigate the effect of α-tocopherol on fibrosis of chronic pancreatitis (CP) rat and explore its mechanism.MethodsMale Wistar rats were randomly divided into control group,acute necrotizing pancreatitis (ANP) group,α-tocopherol group.CP was induced by dibutyltindich loride ( 8 mg/kg) infusion into the tail vein.Gastric lavage of α-tocopherol (800 mg/kg body weight,daily) was started 24 hours after dibutyhindich loride infusion for 4 weeks.The rats in ANP and control group received 0.6 ml salad oil gastric lavage.The rats were sacrificed 4 weeks later.Pancreatic tissue was harvested for histological examination and collagen staining,and measurement of the levels of hydroxyproline and malondialdehyde (MDA) of the pancreas were performed.The mRNA expression of transforming growth factor (TGF)-β１ was measured by real time PCR.ResultsAfter gastric lavage for 4 weeks,the pancreatic tissue inflammation,fiber deposition and abnormal structure in rats of α-tocopherol group were greatly reduced.The levels of MDA and hydroxyproline in rats of α-tocopherol group were significantly lower than those in ANP group [ (0.40 ±0.20) vs (1.07 ±0.41) nmol/100mg,(402.49 ±27.62) vs (664.92 ±29.04) μg/g,P＜0.05].The expressions of TGF-β1 mRNA in rats of o-tocopherol group were significantly lower than those in ANP group (2.24 ± 0.89 vs 3.35 ± 0.66,P ＜ 0.05 ).Conclusions Tocopherol gamma can improve pancreatic inflammation and fibrosis by reducing the oxidative stress level and down-regulating the expression of TGFβ1mRNA in rats with CP.
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Objective To investigate the effect and mechanism of different high concentrations glucose(Glu) on the expression of hypoxia-inducible factor 1α(HIF-1α) in cultured neonatal rat eardiomyocytes under hypoxia and non-hypoxia conditions. Methods Neonatal rat cardiomyocytes were cultured for 6 hours under different conditions and were divided into 6 groups:①Negative control group (5.5 mmol/L Glu) ; ②hypoxia mimicking cobalt chloride(Cocl_2) group(5.5 mmol/L Glu + 400 μmol/L cocl_2 ) ;③Different high concentrations Glu groups: (11.1 mmol/L, 22.2 mmol/L, 33.3 mmol/L Glu);④cocl_2 +different high concentrations Glu groups(11.1 mmol/L Glu +400 μmol/L cocl_2,22.2 mmol/L Glu +400 μmol/L cocl_2, 33.3 mmol/L Glu+400 μmol/L cocl_2);⑤High concentrations Glu + antioxidant α-tocopherol group(33.3 mmol/L Glu + 100 μmol/L α-tocopherol) ; ⑥ High concentrations Glu+antioxidant α-tocopherol+cocl_2 group(33.3 mmol/L Glu+400 μmol/L cocl_2+100 μmol/L α-tocopherol). The effect of high concentrations Glu, cocl_2 and high concentrations Glu plus cocl_2 on the expression of HIF- 1α mRNA and protein in cultured neonatal rat cardiomyocytes, as well as the effect of high concentrations Glu plus antioxidant α-tocopherol, high Glu concentrations plus cocl_2 and antioxidant α-tocopherol on the expression of HIF- 1α mRNA and protein were observed. Results 1. Compared with negative control group(5.5 mmol/L Glu), the 'expression of HIF- 1α was increased under cocl_2 mimicked hypoxia(5.5 mmol/L Glu+400 μmol/L cocl_2, 11.1 mmol/L Glu+400 μmol/L cocl_2 ,22.2 mmol/L Glu+400 μmol/L cocl_2,33.3 mmol/L Glu+400 μmol/L cocl_2). 2. The expression of HIF- 1α was increased gradually after the increasing of Glu concentrations(5.5 mmol/L, 11.1 mmol/L, 22.2 mmol/L and 33.3 mmol/L Glu).3.The expression of HIF-1α was decreased gradually after the increasing of Glu concentrations under certain cocl_2 plus different high concentrations Glu (5.5 mmol/L Glu+400 μmol/L cocl_2, 11.1 mmol/L Glu+400 μmol/L cocl_2, 22.2 mmol/L Glu+400 μmol/L cocl_2,33.3 mmol/L Glu+400 μmol/L cocl_2). 4. Under high concentration Glu plus antioxidant α-tocopherol (33.3 mmol/L Glu+100 μmol/L α-tocopherol) ,the expression of HIF- 1α was less increased than the same high Glu concentration(33.3 mmol/L Glu). 5. Under high Glu concentration plus cocl_2 (33.3 mmol/L Glu+400 μmol/L cocl_2), the expression of HIF- 1α increased less than that of the same high Glu concentration plus antioxidant α-tocopherol and cocl_2 (33.3 mmol/L Glu+400 μmol/L Cocl_2+ 100 μmol/L α-tocopherol). Conclusions High glucose increases the expression of HIF-1α under non-hypoxia, but blunts the expression of HIF-1α under hypoxia in cultured neonatal rat cardiomyocytes. Some mechanisms such as ROS (reactive oxygen species) signal transduction system and oxidative stress may be involved in it.
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The purpose of this study was to investigate the effects of different intensities of exercise on α-tocopherol and thiobarbituric acid reactive substance (TBARS) levels in the plasma and liver of rats. Male Wistar rats were divided into a sedentary control group and exercise groups. The exercise groups were forced to exercise by treadmill running at 30%, 60% and 80% of maximum oxygen uptake (VO<SUB>2</SUB>max) for 120 minutes. Some animals in each exercise group were sacrificed immediately and others at 6 hours after the exercise period, α-Tocopherol levels in the plasma and liver were analyzed by HPLC. Plasma α-tocopherol levels of rats sacrificed immediately after the exercise period decreased significantly in the 60% and 80%VO<SUB>2</SUB>max groups compared to controls. In all exercise groups, plasma α-tocopherol levels were significantly higher 6 hours after the exercise period compared to those sacrificed immediately after the exercise period. Liver a -tocopherol levels were also lower in all exercise groups 6 hours after the exercise period, especially in the 80% VO<SUB>2</SUB>max exercise group. There were no differences in TBARS levels between the control and exercised groups. These results indicate that acute exercise induces oxidative changes in the liver, but the liver is able to compensate by increasing the consumption and release of α-tocopherol to neutralize any damage.
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Purpose To study the effects of α-tocopherol on activator protein-1(AP-1)binding and TGF-β1 expression induced by high glucose in rat mesangial cells and further to clarify the molecular mechanism of antioxidant in treating diabetic nephropathy. Methods AP-1 binding of the rat mesangial cells exposed to high glucose was detected by gel shift assay.The Jun,Fos compositions of AP-1 dimer were determined by supershift assay.Protein expression of TGF-β1 was detected by Western blot.Additionally,the effects of α-tocopherol on AP-1 binding and TGF-β1 expression induced by glucose in rat mesangial cells were also studied. Results High glucose stimulated AP-1 binding of mesangial cells in time-and-dose-dependent manners .This AP-1 binding increase involved JunD and Fos as shown by gel supershift.Glucose also increased protein expression of TGF-β1 at same time.The increased AP-1 binding and TGF-β1 were inhibited with pretreatment with α-tocopherol in glucose-treated mesangial cells. Conclusions This study suggests that α-tocopherol can significantly inhibit AP-1 activity and TGF-β1 expression by glucose in rat mesangial cells,which may be one of its antioxidation mechanisms to retard diabetic nephropathy.
