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OBJECTIVE: To investigate an efficient hydrating facial mask with olive oil (OL)/vitamin E succinate(VES) as the oil phase(O), and with hyaluronic acid, collagen, sodium alginate, arbutin, allantoin as the active ingredients, using a low concentration of surfactant(S) and alcohol-free microemulsion gel as the carrier. METHODS By investigating the effect of VES and co-surfactant (CoS) propylene glycol on microemulsion region, the microemulsion formulation was screened. The microemulsion characteristics of the facial mask were characterized by transmission electron microscopy and Malvern particle size determination. The moisturizing effect and transdermal absorption capacity of the facial mask were evaluated using a commercially available unifon mask as the reference substance. RESULTS Through the compounding of OL and VES, the microemulsion area of OL was increased, and microemulsion range was largest when the mass ratio of OL to VES was 6∶1.The use of the co-surfactant(propylene glycol) reduced the OL microemulsion area. The microemulsion with O/S mass ratio of 4/6 and water content of 85% was selected as the carrier, and the obtained droplet of the facial mask was round, the average particle size was (58.83±0.79) nm, and the PDI was (0.271±0.001), which were in line with the characteristics of microemulsion. Compared with commercial unifon mask, the moisturizing effect of the self-made microemulsion gel facial mask increased by 20.37%. The steady-state infiltration rates of 1% arbutin from the facial mask through the isolated cavy skin was 0.305 mg•cm-2•h-1, which was 4.29 times higher than that from the marketed unifon mask. This product was safe and stable, and meets the sensory and physicochemical indexes of the national light industry standard QB/T2872-2007. CONCLUSION The facial mask with OL/VES microemulsion gel as the carrier can improve the hydrating effect and the transdermal absorption of the active substance, it is expected to be promoted and developed.
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Due to the advantages of polymer micelles and the anticancer activity of doxorubicin (DOX), the polymer micelle of DOX is expected to be used for drug delivery in anticancer applications. As a biocompatible and biodegradable polymer, amphiphilic copolymer heparosan-adipic dihydrazide-vitamin E succinate (KV) can be self-assembled to form micelles with core-shell structure in aqueous phase. In this article, KV conjugates with two different degrees of substitution (DS) were synthesized to load DOX and were characterized by 1H NMR. The size distribution, morphology, zeta potential and release behavior in vitro of the DOX-loaded micelles were studied. In vitro cytotoxicity was investigated by MTT assay against MGC80-3 and COS7 cells. The cellular uptake of the DOX-loaded micelles was observed by fluorescence microscopy and flow cytometry. The 1H NMR spectra results confirmed the KV polymers were successfully conjugated and the degree of VES grafted on heparosan polysaccharide were 12% and 25%. Briefly, the micelles with two different DS were expressed as KV12 and KV25. The DOX-loaded micelles could resist serum adsorption because of the negative charge on the surface. The average particle size measured by dynamic light scattering (DLS) method was 140-150 nm and the TEM results indicated that the morphology of DOX-loaded micelles were spherical. The encapsulation efficiency and drug loading were 80% and 10%-15%, respectively. The DOX-loaded micelles had sustained release behavior and the cumulative release of DOX/KV12 was slightly higher than DOX/KV25. Moreover, the viabilities of cells which were co-incubated with blank micelles were greater than 90%. It is clear that the blank micelles almost non-toxic to both cells. The IC50 of drug-loaded micelles against COS7 cells was much higher than that of MGC80-3 cells and the DOX/KV12 exhibited greater cytotoxicity. The cellular uptake of DOX/KV on MGC80-3 was greater than COS7 cells. In this study, KV polymer micelles have a sustained drug release activity and have a good selectivity to tumor cells, so it would be a potential carrier in drug delivery.
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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 prepare heparan sulfate-vitamin E succinate (HDV) amphipathic copolymers and explore the pharmaceutical properties of doxorubicin (DOX)-loaded HDV copolymer micelles (DOX/HDV). METHODS: HDV copolymers were prepared by amide reaction and its structure was confirmed by H-NMR. DOX/HDV micelles were prepared by ultrasonic method. The particle size, morphology, Zeta potential, drug loading, entrapment efficiency, and in vitro drug release and cytotoxicity were evaluated. RESULTS: HDV amphipathic copolymers were synthesized successfully. The particle size, PDI value and Zeta potential of drug-loaded micelles were (105.0±7.3) nm, (0.239±0.484) and (-21.4±2.6) mV, respectively. The encapsulation and drug loading rate were (76.22±0.76)% and (9.53±0.58)%, respectively. The results of drug release test in vitro showed that DOX was released slowly from the micelles. Cytotoxicity experiments indicated that blank micelles had no apparent toxicity against both tumor cells and normal cells. However, DOX/HDV micelles could inhibit the tumor cells growth obviously. CONCLUSION: HDV copolymers can effectively load DOX with properties of drug sustained release and enhanced cytotoxicity against tumor cells in vitro, which indicates that HDV may be a potential candidate for cancer therapy.
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OBJECTIVE: To enhance the anticancer activity of doxorubicin(DOX) by conjugating DOX and vitamin E succinate (VES) and loading the conjugate into hyaluronic acid-octadecylamine (HA-C18) copolymer micelles. METHODS: DOX and VES were conjugated by amide reaction. DOX-VES/HA-C18micelles were prepared via a probe-type ultrasonication technique. The morphology of the micelles was determined using a transmission electron microscopy (TEM).Dynamic light scattering (DLS) technique was used to determine the particle size distribution, hydrodynamic diameters, and stability of the micelles. Ultracentrifugation was exploited for measuring the drug loading (DL) and encapsulation efficiency (EE), and the in vitro release was investigated using a dialysis tubing. The cellular uptake and cellular distribution of drug-loaded micelles in MCF-7 cells were observed by fluorescence microscope, and the fluorescence intensity of DOX was evaluated by flow cytometer. The cytotoxicity of free DOX and drug-loaded micelles was tested by MTT assay against MCF-7 cells. RESULTS: DOX-VES/HA-C18 showed a nearly spherical morphology and good stability in PBS (pH 7.4) and 10% FBS. The particle size and zeta potential were (184.6±9.42) nm and (-20.7±1.23) mV, respectively. The DL and EE were (15.8±2.85)% and (94.2±1.32)%, respectively. DOX-VES/HA-C18had a good controlled drug release property. Furthermore, DOX-VES/HA-C18with accumulation in nucleipresented higher anti-tumor activity than free DOX and DOX/HA-C18. CONCLUSION: DOX-VES conjugate has synergistic anti-tumor effect and good application prospects.
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Objective: To study the inhibitory and apoptosis-inducing effect of vitamin E succinate (VES) on androgen-independent prostate cancer cell line PC-3 in vitro. Methods: VES was dissolved with ethanol to obtain VES solution. PC-3 cells of logarithmic growth phase were treated with various concentrations of VES solution (25, 50, 75, 100, and 125mg/L); cells in control group were treated with 1.25% ethanol. MTT method was used to measure the viability and inhibitory rate of cells in each group 24h, 48h and 72h after VES treatment; flow cytometry was employed to determine the apoptosis rate of the PC-3 cells. Results: The viability of cells in the experimental groups was significantly lower than that in the control group (P<0.05). The viability of cells in the experimental groups was negatively correlated with the concentration and exposure period of VES solution; the viability of cells in the control group was positively correlated with the exposure period of VES solution. The apoptosis rate of cells in the experimental groups was much higher than that in the control group; the rate in the experimental group was positively correlated with the concentration and exposure period of VES solution. The optimal induction of apoptosis was achieved af ter 48 h exposure to 75 mg/L VES solution, with a apoptosis rate above 80%. Conclusion: VES can inhibit the proliferation of PC-3 cells and can induce apoptosis of them, which casts new lights on prevention and treatment of prostate cancer.
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Objective: To investigate the effect of vitamin E succinate (VES) on apoptosis of Tca 8113 human oral squamous carcinoma cells and its action mechanism. Methods: Flow cytometry was applied to determine the effect of VES on cell cycle distribution and apoptosis after PI staining or Annexin V/PI double staining. The expression of Bax mRNA was quantified by RT-PCR. The relative amounts of the Bax protein was measured by Western blotting. Results: VES significantly inhibited the growth of Tca8113 cells, induced typical apoptosis, and up-regulated the expression of Bax mRNA and protein. After 24 h the apoptotic rate reached the peak level. Conclusion: VES induces apoptosis of Tca8113 human oral squamous carcinoma cells, which is probably related with up-regulation of Bax expression.
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Objective: To investigate the growth inhibition and apoptosis induction effect of vitamin E succinate (VES) on human colon cancer cells and to analyze the modulation of apoptosis-mediator Fas expression in this process. Methods: Human colon cancer cell line LS174T was treated with VES for 12 h, 24 h and 48 h at the concentrations of 5 mg/L, 10 mg/L and 20mg/L. 1-(4,5-dimethylthiazo-2-yl)-3,5-diphenylformazan (MTT) assay was employed to detect the inhibitory effect of VES on the growth of colon cancer cells. Flow cytometry was then used to analyze the cell cycle of the colon cancer cells after being treated with VES and the apoptotic rate was calculated at the same time. To find out whether the Fas protein expression was modulated in this process, Western blotting assay and flow cytometry were used to detect the Fas protein level in whole cell lystates and on cell surface. Results: VES exhibited a significant inhibitory effect on the growth of human colon cancer cells in a doseand time-dependent manner. After being treated with VES at 5 mg/L, 10 mg/L and 20 mg/L for 48 h, the apoptotic rate of LS174T cells rose from 0.90% to 15.9%, 46.7% and 64.5%, respectively. Fas neutralizing antibody can significantly block VES-induced apoptosis. After the administration of VES, total Fas protein in whole-cell extracts increased in a dose-dependent manner. The flow cytometry showed that the mean fluorescence intensity rose from 5.43 to 9.88, 13.21 and 18.0 after being treated with VES. Conclusion: VES can induce significant growth inhibition and apoptosis in human colon cancer cells. The modulation of Fas expression is one of the mechanisms involved in this process and may be related to the upregulation of Fas molecule on the cancer cell surface.
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Objective: To investigate the growth inhibition and apoptosis induction effect of vitamin E succinate (VES) on human colon cancer cells and to analyze the modulation of apoptosis-mediator Fas expression in this process. Methods: Human colon cancer cell line LS174T was treated with VES for 12 h, 24 h and 48 h at the concentrations of 5 mg/L, 10 mg/L and 20mg/L. 1-(4,5-dimethylthiazo-2-yl)-3,5-diphenylformazan (MTT) assay was employed to detect the inhibitory effect of VES on the growth of colon cancer cells. Flow cytometry was then used to analyze the cell cycle of the colon cancer cells after being treated with VES and the apoptotic rate was calculated at the same time. To find out whether the Fas protein expression was modulated in this process, Western blotting assay and flow cytometry were used to detect the Fas protein level in whole cell lystates and on cell surface. Results: VES exhibited a significant inhibitory effect on the growth of human colon cancer cells in a doseand time-dependent manner. After being treated with VES at 5 mg/L, 10 mg/L and 20 mg/L for 48 h, the apoptotic rate of LS174T cells rose from 0.90% to 15.9%, 46.7% and 64.5%, respectively. Fas neutralizing antibody can significantly block VES-induced apoptosis. After the administration of VES, total Fas protein in whole-cell extracts increased in a dose-dependent manner. The flow cytometry showed that the mean fluorescence intensity rose from 5.43 to 9.88, 13.21 and 18.0 after being treated with VES. Conclusion: VES can induce significant growth inhibition and apoptosis in human colon cancer cells. The modulation of Fas expression is one of the mechanisms involved in this process and may be related to the upregulation of Fas molecule on the cancer cell surface.
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AIM: To study the antiproliferation of vitamin E succinate (VES) on pterygium fibroblasts in vitro and to find a potential agent for prevention and treatment of primary and recurrence pterygium.METHODS: Primary culture and subculture of pterygium fibroblasts were established in vitro ,and different concentrations of VES (0, 10 and 20mg/L) were added to subcultured fibroblasts, respectively. Influence of VES on the growth curve of fibroblast was observed at day 2, 4 and 7 after treatment of VES. 3- [4,5-Dimethylthiazolzyl]-2,5-Diphenyl Tetrazolium Bromide (MTT) assay at 490nm was used to evaluate the effect of the cells proliferation.RESULTS: The addition of VES to culture caused the marked descent of growth curve in comparison with the control group, and the inhibiting rate of 10 and 20mg/L of VES was 33.2% and 46.7%, 67.9%, and 76.8%, 81.7% at day 2,4 and 7, respectively. VES could obviously inhibit the fibroblast proliferation in dose-dependent manner by MTT assay.CONCLUSION: VES can significantly inhibit the proliferation of pterygium fibroblast in vitro.
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Objective: To investigate the growth inhibition and apoptosis induction effect of vitamin E succinate (VES) on human colon cancer cells and to analyze the modulation of apoptosis-mediator Fas expression in this process. Methods: Human colon cancer cell line LS174T was treated with VES for 12 h, 24 h and 48 h at the concentrations of 5 mg/L, 10 mg/L and 20mg/L. 1-(4,5-dimethylthiazo-2-yl)-3,5-diphenylformazan (MTT) assay was employed to detect the inhibitory effect of VES on the growth of colon cancer cells. Flow cytometry was then used to analyze the cell cycle of the colon cancer cells after being treated with VES and the apoptotic rate was calculated at the same time. To find out whether the Fas protein expression was modulated in this process, Western blotting assay and flow cytometry were used to detect the Fas protein level in whole cell lystates and on cell surface. Results: VES exhibited a significant inhibitory effect on the growth of human colon cancer cells in a doseand time-dependent manner. After being treated with VES at 5 mg/L, 10 mg/L and 20 mg/L for 48 h, the apoptotic rate of LS174T cells rose from 0.90% to 15.9%, 46.7% and 64.5%, respectively. Fas neutralizing antibody can significantly block VES-induced apoptosis. After the administration of VES, total Fas protein in whole-cell extracts increased in a dose-dependent manner. The flow cytometry showed that the mean fluorescence intensity rose from 5.43 to 9.88, 13.21 and 18.0 after being treated with VES. Conclusion: VES can induce significant growth inhibition and apoptosis in human colon cancer cells. The modulation of Fas expression is one of the mechanisms involved in this process and may be related to the upregulation of Fas molecule on the cancer cell surface.
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Objective:To study the inhibitory and apoptosisinducing effect of vitamin E succinate(VES) on androgen-independent prostate cancer cell line PC-3 in vitro.Methods: VES was dissolved with ethanol to obtain VES solution.PC-3 cells of logarithmic growth phase were treated with various concentrations of VES solution(25,50,75,100,and 125mg/L);cells in control group were treated with 1.25% ethanol.MTT method was used to measure the viability and inhibitory rate of cells in each group 24h,48h and 72h after VES treatment;flow cytometry was employed to determine the apoptosis rate of the PC-3 cells.Results: The viability of cells in the experimental groups was significantly lower than that in the control group(P
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Objective:To investigate the antitumor effect of vitamin E succinate combined with tamoxifen on the graft model of human breast cancer in nude mice and to analyze the possible mechanism.Methods: MCF-7 human breast cancer cells were inoculated subcutaneously in 40 nude mice.Then the mice were equally divided into 4 groups: blank control group(non-treatment),TAM treatment group(5 mg/kg),VES treatment group(150 mg/kg) and the TAM+VES treatment group(TAM 5 mg/kg +VES 150 mg/kg).The size of the tumor was measured and both the cell cycle and cell surface Fas/FasL were determined by flow cytometry 4 weeks after treatment.Fas/FasL expression in tumor tissue was detected with immunohistochemistry and cell apoptosis was detected by TUNEL method.Results: The co-administration of VES and TAM had more potent inhibitory effect on the growth of solid tumor than VES or TAM administered alone(P
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AIM To study the effects of vitamin E succinate (VES) on the cell growth and the DNA synthesis of human gastric carcinoma cell (SGC 7901). METHODS The growth curve was determined with counting viable cell numbers. The colony formations were counted with Giemsa dye staining. The cell cycle was analyzed using flow cytometry (FCM) and the DNA synthesis was observed with the 3H TdR incorporation method. RESULTS VES could inhibit the growth and colony formation of SGC 7901 cells. Growth curve display:after SGC 7901 cells were treated with 5 mg?L -1 、10 mg?L -1 and 20 mg?L -1 VES for seven days, the inhibition rate are 41 2%、98 3% and 100%, respectively. The colony formation of SGC 7901 cell at 24 h was inhibited 6 7%、50 4%、87 2%, and at 48 h was 24 7%、73 4%、100%, respectively. FCM analysis revealed that VES could decrease the percentage of cells in G 2 M phase after treated 48 h in a dose dependent manner, while increase the percentage of cells in S pheise. The assays of 3H TdR incorporation into DNA showed obvious inhibition dose dependently after exposure to VES for 48 h. CONCLUSION VES could inhibit gastric carcinoma cell growth by arresting DNA synthesis in vitro .