Currently, multidrug resistance (MDR) is one of the major reasons for failure in clinical cancer chemotherapy. Overexpression of the ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which significantly increases the efflux of anticancer drugs from tumor cells, enhances MDR. In the past few decades, four generations of P-gp inhibitors have appeared. However, they are limited in clinical application due to their severe toxic side effects. As a P-gp inhibitor and carrier for loading chemotherapy agents, TPGS has received increasing attention due to its advantages and unique properties of reversing MDR. TPGS is an amphipathic agent that increases the solubility of most chemotherapy drugs and decreases severe side effects. In addition, TPGS is an excellent carrier with P-gp-inhibiting ability. In this review, we summarize the latest articles on TPGS-based nanodelivery systems to prevent MDR.

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Vitamin E deficiencies can impact normal growth and development in humans and animals, and assessment of circulating levels of vitamin E and its metabolites may be an important endpoint for evaluation. Development of a sensitive method to detect and quantify low concentrations of vitamin E and metabolites in biological specimens allows for a proper diagnosis for patients and animals that are deficient. We developed a method to simultaneously extract, detect, and quantify the vitamin E compounds alpha-tocopherol (α-TP), gamma-tocopherol (γ-TP), alpha-tocotrienol (α-TT), and gamma-tocotrienol (γ-TT), and the corresponding metabolites formed after β-oxidation of α-TP and γ-TP, alpha-carboxymethylbutyl hydroxychroman (α-CMBHC) and alpha- or gamma-carboxyethyl hydroxychroman (α- or γ-CEHC), respectively, from equine plasma and serum. Quantification was achieved through liquid chromatography-tandem mass spectrometry. We applied a 96-well high-throughput format using a Phenomenex Phree plate to analyze plasma and serum. Compounds were separated by using a Waters ACQUITY UPLC BEH C18 column with a reverse-phase gradient. The limits of detection for the metabolites and vitamin E compounds were 8-330 pg/mL. To validate the method, intra-day and inter-day accuracy and precision were evaluated along with limits of detection and quantification. The method was then applied to determine concentrations of these analytes in plasma and serum of horses. Alpha-TP levels were 3-6 µg/mL of matrix; the metabolites were found at much lower levels, 0.2-1.0 ng/mL of matrix.

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Background: Throughout the past decade, Pickering emulsion has been increasingly utilized for the encapsulation of bioactive compounds due to its high stability and biocompatibility. In the present work, palm tocotrienols were initially encapsulated in a calcium carbonate Pickering emulsion, which was then subjected to alginate gelation and subsequent chitosan coating. The effects of wall material (alginate and chitosan) concentrations, gelation pH and time, and chitosan coating time on the encapsulation efficiency of palm tocotrienols were explored.

Results: Our findings revealed that uncoated alginate microcapsules ruptured upon drying and exhibited low encapsulation efficiency (13.81 ± 2.76%). However, the addition of chitosan successfully provided a more complex and rigid external wall structure to enhance the stability of the microcapsules. By prolonging the crosslinking time from 5 to 30 min and increasing the chitosan concentration from 0.1% to 0.5%, the oil encapsulation efficiency was increased by 28%. Under the right gelation pH (pH 4), the extension of gelation time from 1 to 12 h resulted in an increase in alginate-Ca²⁺ crosslinkings, thus strengthening the microcapsules.

Conclusion: With the optimum formulation and process parameters, a high encapsulation efficiency (81.49 ± 1.75%) with an elevated oil loading efficiency (63.58 ± 2.96%) were achieved. The final product is biocompatible and can potentially be used for the delivery of palm tocotrienols. © 2021 Society of Chemical Industry.

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In this study, we investigated the compositions of vitamin E tocochromanol [tocopherol (Toc) and tocotrienol (T3)] in crude and refined rice bran oil (RBO) produced in Japan and other countries, including Brazil, Thailand, and Vietnam, based on high-performance liquid chromatography analysis. All RBO analyzed contained α-, β- and γ-Toc and α-, γ- and δ-T3. Japanese crude RBO, although not refined RBO, also contained β-T3. Furthermore, total Toc contents in both Japanese crude and refined oils were found to be higher than those in the crude and refined RBO from other countries. Total T3 contents in Japanese crude RBO were similar to those in the crude RBO from Brazil and Vietnam. The α-Toc and α-T3 contents in Japanese crude and refined RBO were considerably higher than those in the crude and refined RBO produced in other countries, whereas in contrast, γ-Toc and γ-T3 contents in Japanese crude and refined RBO were lower. Consequently, the ratios of total α-Toc and α-T3 contents to total γ-Toc and γ-T3 contents in Japanese crude and refined RBO (1.75 and 1.91, respectively) were notably higher than those in the crude and refined RBO produced in other countries. Similarly, the ratios of total Toc to total T3 in Japanese crude and refined RBO were higher than those in the crude and refined RBO produced in other countries. These results accordingly indicate that the ratio of total α-Toc and α-T3 contents to γ-Toc and γ-T3 contents could be used as an effective index to discriminate between the RBO produced in Japan and that produced in other countries.

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Calcium carbonate (CaCO₃) has been utilized as a pH-responsive component in various products. In this present work, palm tocotrienols-rich fraction (TRF) was successfully entrapped in a self-assembled oil-in-water (O/W) emulsion system by using CaCO₃ as the stabilizer. The emulsion droplet size, viscosity and tocotrienols entrapment efficiency (EE) were strongly affected by varying the processing (homogenization speed and time) and formulation (CaCO₃ and TRF concentrations) parameters. Our findings indicated that the combination of 5000 rpm homogenization speed, 15 min homogenization time, 0.75% CaCO₃ concentration and 2% TRF concentration resulted in a high EE of tocotrienols (92.59-99.16%) and small droplet size (18.83 ± 1.36 µm). The resulting emulsion system readily released the entrapped tocotrienols across the pH range tested (pH 1-9); with relatively the highest release observed at pH 3. The current study presents a potential pH-sensitive emulsion system for the entrapment and delivery of palm tocotrienols.

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Potential benefit of microencapsulation is its ability to deliver and protect incorporated ingredients such as vitamin E. Microcapsule wall properties can be changed by adding of coss-linking agents that are usually considered toxic for application. The microcapsules were prepared by a spray-drying technique using coacervation method, by depositing the coacervate formed in the mixture of chitosan and sodium lauryl ether sulfate to the oil/water interface. All obtained microcapsules suspensions had slightly lower mean diameter compared to the starting emulsion (6.85 ± 0.213 μm), which shows their good stability during the drying process. The choice and absence of cross-linking agents had influence on kinetics of vitamin E release. Encapsulation efficiency of microcapsules without cross-linking agent was 73.17 ± 0.64 %. This study avoided the use of aldehydes as cross-linking agents and found that chitosan/SLES complex can be used as wall material for the microencapsulation of hydrophobic active molecules in cosmetic industry.

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The consumption of vegetable oil is an important way for the body to obtain tocols. However, the impact of oil types and grades on the tocopherol and tocotrienol contents in vegetable oils is unclear. In this study, nine types of traditional edible oils and ten types of self-produced new types of vegetable oil were used to analyze eight kinds of tocols. The results showed that the oil types exerted a great impact on the tocol content of traditional edible oils. Soybean oils, corn oils, and rapeseed oils all could be well distinguished from sunflower oils. Both sunflower oils and cotton seed oils showed major differences from camellia oils as well as sesame oils. Among them, rice bran oils contained the most abundant types of tocols. New types of oil, especially sacha inchi oil, have provided a new approach to obtaining oils with a high tocol content. Oil refinement leads to the loss of tocols in vegetable oil, and the degree of oil refinement determines the oil grade. However, the oil grade could not imply the final tocol content in oil from market. This study could be beneficial for the oil industry and dietary nutrition.

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High-performance chromatography method was developed and validated for essaying α-tocopherol and cholesterol in cryopreservation media. Chromatographic separation was performed on isocratic system, using a C-18 column. The mobile phase was composed of a mixture of methanol: acetonitrile: water 68:28:4 (v/v/v), using a flow rate of 1.5 ml/min and 20 μl injection volume, at a wavelength of 208 nm. The method was validated according to ICH guidelines. The method proved to be specific, accurate, precise and linear with correlation coefficients greater than 0.996 over a wide concentration range of both analytes. Vitamin E and cholesterol presented limits of detection of 0.002 mg/ml, 0.026 mg/ml and limits of quantitation of 0.006 mg/ml, 0.086 mg/ml, respectively. This method shows simple, rapid, high precision and accuracy and offers the advantage of simultaneous assay of vitamin E and cholesterol (alone, in cyclodextrins complexes or in liposome loaded) on semen cryopreservation media.

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Delta-tocotrienol as a vitamin E isomer has received much attention because of its diverse biomedical applications. Microbial biosynthesis of delta-tocotrienol is a promising strategy for its economic and environmental advantages. Here, we accomplished complete biosynthesis of delta-tocotrienol in Saccharomyces cerevisiae from glucose. We first constructed and incorporated a heterologous pathway into the genome of S. cerevisiae by incorporating the genes hpd (from Pseudomonas putida KT2440), hpt (from Synechocystis sp. PCC 6803), and vte1 (from Arabidopsis thaliana) for the biosynthesis of delta-tocotrienol. We further enhanced the biosynthesis of the precursor geranylgeranyl diphosphate by overexpressing the thmg1 and ggppssa (from Sulfolobus acidocaldarius) genes, leading to a production titer of delta-tocotrienol of 1.39 ± 0.01 mg/L. Finally, we optimized the fermentation medium using the response surface methodology, enabling a high-titer production of delta-tocotrienol (3.56 ± 0.25 mg/L), ∼2.6-fold of that of the initial culture medium. Fed-batch fermentation in a 2 L fermenter was further used to enhance the production titer of delta-tocotrienol (4.10 ± 0.10 mg/L). To the best of our knowledge, this is the first report on the de novo biosynthesis of delta-tocotrienol in S. cerevisiae, and the highest titer obtained for microbial production of delta-tocotrienol.

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