Tocofersolan

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis

Objectives: D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis. Methods: Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides). Results: Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported. Conclusions: Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

Progress in the study of D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) reversing multidrug resistance

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.

Recent developments in d-α-tocopheryl polyethylene glycol-succinate-based nanomedicine for cancer therapy

Cancer remains an obstacle to be surmounted by humans. As an FDA-approved biocompatible drug excipient, d-α-tocopheryl polyethylene glycol succinate (TPGS) has been widely applied in drug delivery system (DDS). Along with in-depth analyses of TPGS-based DDS, increasingly attractive results have revealed that TPGS is able to act not only as a simple drug carrier but also as an assistant molecule with various bio-functions to improve anticancer efficacy. In this review, recent advances in TPGS-based DDS are summarized. TPGS can inhibit P-glycoprotein, enhance drug absorption, induce mitochondrial-associated apoptosis or other apoptotic pathways, promote drug penetration and tumor accumulation, and even inhibit tumor metastasis. As a result, many formulations, by using original TPGS, TPGS-drug conjugates or TPGS copolymers, were prepared, and as expected, an enhanced therapeutic effect was achieved in different tumor models, especially in multidrug resistant and metastatic tumors. Although the mechanisms by which TPGS participates in such functions are not yet very clear, considering its effectiveness in tumor treatment, TPGS-based DDS appears to be one of the best candidates for future clinical applications.

Vitamin E D-α-tocopheryl polyethylene glycol 1000 succinate-based nanomedicine

Recent Advances of D-α-tocopherol Polyethylene Glycol 1000 Succinate Based Stimuli-responsive Nanomedicine for Cancer Treatment

D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA. It's widely applied as a multifunctional drug carrier for nanomedicine. The advantages of TPGS include P-glycoprotein (P-gp) inhibition, penetration promotion, apoptosis induction via mitochondrial-associated apoptotic pathways, multidrug resistant (MDR) reversion, metastasis inhibition and so on. TPGS-based drug delivery systems which are responding to external stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect, through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior. In this review, TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed, including pH-responsive, redoxresponsive and multi-responsive systems in various formulations. The achievements, mechanisms and different characteristics of TPGS-based stimuli-responsive drug-delivery systems in tumor therapy were also outlined.