Amelioration of Acrylamide Induced Neurotoxicity in Wistar Rats

Present study was undertaken to study the neurotoxicity of oral acrylamide (ACR) and its amelioration using α-tocopherol, reduced glutathione (GSH) and hot aqueous extract (HAE) of Ocimum sanctum. Forty five male Wistar rats were divided into 12 groups. The study showed a significant reduction in the body weight of the rats fed with ACR in comparison to the other groups while body weight was restored in the rats fed with α-tocopherol and HAE. Neurotoxicity in rats fed with ACR was evident with the results of histopathology and oxidative stress (high MDA and decreased activities of GSH, SOD, GST and CAT in brain). Co-administration of α-tocopherol and HAE lowered these changes however, there was no marked improvement seen in neural damage but improvement was evident in behavioral as well as physiological changes at a marked point. Histopathology of brain in ACR alone fed group showed extensive neural degeneration and massive deposition of fibrin which was substantially decreased and ameliorated with the co-administration of α-tocopherol and HAE. These results support the oxidative stress results as well. Our results suggests that α-tocopherol and HAE can be useful for protecting brain tissue against ACR induced neurotoxicity through minimizing the free radical mediated oxidative stress

Heat Degradation of α-Tocopherol in Sri Lankan Commercially available Palm Olein

Objectives: Palm olein, which is the fractionated form of palm oil, is commonly used as cooking oil in Sri Lanka. Processing of crude oil degrades α-tocopherol as does exposure to high heat during cooking. This study was aimed to determine the content and heat degradation of α-tocopherol in Sri Lankan commercially available palm olein. Method: Four different brands of Sri Lankan commercially available palm olein (100 mL) were heated to 180°C for 10 minutes. The oil was subsequently cooled and re-heated five times and assayed in duplicate. Between each cycle of re-heating oil was left in room temperature to cool for 5 hours. Fresh palm olein and the heated samples were analyzed for α-tocopherol content using reversed-phase High-pressure liquid chromatography (HPLC) (Shimadzu, Japan). Results: The mean α-tocopherol content in unheated palm olein was 3.02 ± 0.35 ppm, with no significant differences between brands. Heating Palm olein for 10 minutes resulted in 56.6% reduction in α-tocopherol compared to unheated oil. Re-heating resulted in further reduction with a 100% loss by the fourth time. Conclusion: The Sri Lankan commercially available palm olein did not provide expected α-tocopherol content, and is not a good source of dietary α-tocopherol. Further analysis is required to quantify α-tocopherol content. Since re-heating further reduced α-tocopherol levels, repeated frying during cooking is likely to result in a minimal level of α-tocopherol being provided through palm olein to the diet.

Construction and Preliminary Evaluation of Lipid Complex of siRNA Modified by D-α-tocopheryl Poly (2- ethyl-2-oxazoline) Succinate / 中国药学杂志

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.

Preparation and characteristics of TPGS-CS/PTX polymeric micelles and its in vivo intestines absorption in rats / 中草药

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.

Preparation and evaluation of GEN-VES-TPGS1000 nano-micelles / 中草药

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.

Preparation of TPGS-modified artesunate liposomes and their in vitro anti-tumor activity / 中成药

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.

Dioxygen reduction, reduced oxygen species, oxygen toxicity and antioxidants — A commentary.

Molecular oxygen, a diradical, needs intervention of redox metal ions or other radicals to receive electrons for its reduction. The oxygen radicals thus produced are responsible for oxygen toxicity and oxidative stress. But, autoxidation, relevant in ischemia-reperfusion injury, is absent in any discussion on oxygen toxicity. Naturally occurring compounds which prevent formation or action of the reactive oxygen species (ROS) are generally referred as antioxidants. The reduced oxygen species, superoxide, peroxide and hydroxyl radicals, are formed in a variety of systems in the cell and are useful in selective oxidations. Currently, the popular method for assaying ROS with fluorescence of dichlorofluorescein actually measures a hemeprotein-Fe-oxo complex. The Fe-oxyl radicals are the likely oxidants in damaging proteins, nucleic acids and lipids. Such major lesions are normally repaired or replaced in the cells. The antioxidants counter the damaging oxidant actions. Among these, occurring in large concentration, are glutathione and ubiquinol, synthesized in the body and ascorbic acid and α-tocopherol, drawn from the food. A large number of plant-derived phenolic compounds, especially the flavonoid variety, are also absorbed, albeit poorly, from the food. At the natural low concentrations, these compounds show wide ranging biological effects. Increased benefit on increasing them in circulating blood needs individual verification. The polyphenolic compounds demonstrated powerful antioxidant effects in laboratory experiments. But the clinical studies did not support the consequent expectations of countering the oxidative stress, the purported crucial factor in pathology in several diseases. Antioxidant action against ROS causing oxygen toxicity needs to be reassessed. This commentary is a reappraisal of formation and reactivity of ROS in different cells, the active cellular oxidant forms, products of oxidant action on proteins, nucleic acids and lipids as marker of oxidant injury, bulk antioxidants of endogenous and exogenous origin, limited absorption occurrence and functions of polyphenolic classes.

Gingival absorption of α-tocopherol acetate and 18β-glycyrrhetinic acid : in vitro evaluation in reconstructed gingival tissue / 대한구강보건학회지

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.

Chemical constituents from leaves of Adinandra nitida / 中草药

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.

Chemical constituents of Pilea sinofasciata / 中草药

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.

Antinociceptive and Anti-inflammatory Effects of Combined Administration of a-tocopherol and Diclofenac.

Background: Nonsteroidal anti-inflammatory drugs such as diclofenac are used for relief of pain and inflammation, but frequently cause gastrointestinal complications. This study aimed to explore that combination of diclofenac and α-tocopherol (αT) are better analgesic as well as anti-inflammatory agent than that of diclofenac alone. Objective: To assess the effects of combination of diclofenac with α-tocopherol on pain and inflammation. Methods: This prospective experimental study was conducted in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka between January to December 2013. For this purpose, 15 male Long Evans rats were studied. On the basis of vitamin and drug administrations, the rats were divided into three (3) groups (5 rats in each). Control group received normal saline, one experimental group received diclofenac sodium (DS) at a dose of 10 mg/kg/body weight, and another experimental group received combination of DS with αT at a dose of 10 mg/kg/body weight and 500mg/kg/body weight, respectively. All the groups received single dose and equal volume (1 ml) through intraperitoneal route 1 hour before the test. Just one hour after administrations, they were subjected to formalin test followed by formalin induced paw edema test. The data were statistically analyzed by ANOVA followed by Bonferroni Post Hoc test. Results: Combined administration of DS and αT significantly (p<0.001) lowered the variables for nociceptive pain, central analgesic activity, inflammatory pain and inflammation than individual intervention of DS. Conclusion: From this study it may be concluded that, combined administration of diclofenac sodium and ±-tocopherol were more effective in lowering pain and inflammation than individual administration of diclofenac.

Preparation of colchicine ethosomes containing TPGS and in vitro transdermal permeation / 中草药

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.

Study on antioxidant of ethyl polyenoate soft capsules / 中国生化药物杂志

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.

Effect of D-α-tocopherol polyethylene glycol 1000 succinate on inhibition of MCF-7 cell proliferation by baohuoside I / 中草药

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.

Advance in application of D-α-tocopherol polyethyleneglycol succinate in the field of pharmaceutics / 中国药学杂志

OBJECTIVE: To review the applications of D-α-tocopherol polyethylene glycol succinate (TPGS) as a drug carrier in pharmaceutical preparation.

Protective effect of α-tocopherol succinate against early hematopoietic injury in mice with acute radiation sickness / 解放军医学杂志

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.

Evidences for Deleterous Role of Free Radicals in Experimental Varicocele Using Animal Model.

Aim: It is highly intricate to categorize a solitary or prevailing factor for pathophysiology of varicocele. Herein, the basis of free radicals in the pathogenesis of varicocele was assessed. Study Design: Experimental using animal models. Place and Duration of Study: Department of Anatomy, College of Medicine, Lagos State University, Ikeja, Lagos, Nigeria, between April, 2012 and August, 2012. Methodology: Five (5) groups of rats were used, Group A animals served as the control, while Groups B, C, D and E animals were varicocelized. Groups C, E and E in addition, had intramuscular treatment of 25 mg/kg, 50 mg/kg and 75mg/kg body weight of α-tocopherol respectively. The models were sacrificed on 65th day and Testicular weights and volumes, sperm parameters, histology, morphometry, enzymatic and non enzymatic antioxidants were vastly estimated. Result: There was a significant (p<0.05) increase in activity level of SOD (5.92±4.1), CAT (380.2±7.1) and GPx (0.79±0.8) and a reduced lipid peroxidation evidenced by significant (p<0.05) reduction in level of MDA (18.2±6.1) of the varicocelized rat treated with Vitamin E (75mg/kg b.wt.) when compared to the activity of SOD (3.31±4.1), CAT (361.2±4.5), GPx (0.36±6.1) and MDA (0.36±6.1) of untreated varicocelized models. The geometric values, sperm characteristics and histological profiles threaded the same pattern as the oxidative status. Conclusion: These results confirmed and validated the important role of reactive oxygen in the pathogenesis of varicocelized.

Effect of (+)-catechin hydrate on oxidative stress induced by high sucrose and high fat diet in male Wistar rats.

Increased lipid peroxidation and reduced glutathione levels in liver of rats fed high sucrose high fat (HSHF) diet were normalized by concomitant administration of (+)-catechin hydrate. Plasma non-enzymatic antioxidants viz. α-tocopherol, ascorbic acid and total thiols decrease were also significantly less in rats administered with (+)-catechin hydrate concomitantly with HSHF diet. Thus the present results indicate that (+)-catechin hydrate has antioxidant activity and is effective in reducing oxidative stress. The study is of clinical importance as oxidative stress is known to be the cause of many clinical manifestations viz. cancer, Parkinson’s disease, atherosclerosis, heart failure, myocardial infarction and many other diseases.

Protective effect of -tocopherol against hematotoxicity, hepatotoxicity and nephrotoxicity induced by nickel sulfate in male albino rats.

Among the chemical hazards, heavy metal like nickel (Ni) is considered to be a serious one. It induces severe liver and kidney damage by altering several marker enzymes and ascorbate-cholesterol metabolism. The objective of the study was to investigate the possible protective role of α-tocopherol on NiSO4 (Ni II) exposed alteration of hematological parameters, markers of liver and kidney functions, hepatic and renal antioxidant defense system in male albino rats. We have studied the effects of α-tocopherol supplementation on nickel sulfate induced alteration of body weight, hematology, liver and kidney toxicity markers (SGOT, SGPT, total protein, urea, creatinine) and hepatic and renal antioxidant defense system of male albino rats. Nickel toxicity results in decreased body weight gain and relative liver and kidney weight. Nickel treatment also resulted in alteration of hematological parameters along with increased liver and kidney toxicity markers. Nickel sulfate administration significantly increased the level of lipid peroxides and decreased antioxidant enzyme activities in hepatic and renal tissue. Simultaneous treatment with á-tocopherol exhibited a possible protective role on the toxic effect of nickel on body and organ weights, hematological parameters, SGPT activity and improved tissue antioxidant defense system. α-tocopherol, may partially prevent nickel induced alteration of hematological and biochemical parameters as well as have amelioratic effects on nickel induced alteration of antioxidant status of liver and kidney.

Preparation of paclitaxel-loaded mixed micelles and its in situ absorption in rat intestine / 中国药学杂志

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.