CLINICAL REFERENCES

THE SCIENCE OF VITAMIN E TPGS

The properties, functions, efficacy, applications, and safety of Vitamin E TPGS have been documented in studies conducted by leading researchers world-wide. These studies including clinical animal and human studies have been reported in refereed scientific journals and presented at scientific conferences. Below are selected references which document the efficacy and safety of vitamin E TPGS. These references are grouped to document the properties, mechanism of action, functions, product applications and safety.


Emerging Science and Novel Applications

  1. Zhang, Zhiping et al. (2013). The applications of Vitamin E TPGS in drug delivery. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 49. 10.1016/j.ejps.2013.02.006.

  2.  Zhang, Zhiping et al. (2018). Recent Advances in the Application of Vitamin E TPGS for Drug Delivery. Theranostics. 8. 464-485. 10.7150/thno.22711.

  3.  Papas, Andreas. (2021). Vitamin E TPGS and its applications in nutraceuticals. 10.1016/B978-0-12-821038-3.00059-8.

  4. Zhou, X.-X & Song, S.-S & Wang, D.-K. (2012). Advantages of vitamin E TPGS and its P-glycoprotein-inhibiting mechanism. Chinese Journal of New Drugs. 21. 2758-2762.The applications of Vitamin E TPGS in drug delivery. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.The applications of vitamin E TPGS in drug delivery. European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences.


Physical Properties, Emulsifier, Solubilizer, and Formulation Excipient

  1. Sadoqi M, Lau-Cam CA, Wu SH. Investigation of the micellar properties of the tocopheryl polyethylene glycol succinate surfactants TPGS 400 and TPGS 1000 by steady state fluorometry. J Colloid Interface Sci. 2009 May 15;333(2):585-9.

  2. Mudra DR, Borchardt RT. Absorption barriers in the rat intestinal mucosa. Effects of polyethoxylated solubilizing agents on drug permeation and metabolism. J Pharm Sci. 2009 Jul 31.

  3. Ke WT, Lin SY, Ho HO, Sheu MT. Physical characterizations of microemulsion systems using tocopheryl polyethylene glycol 1000 succinate (TPGS) as a surfactant for the oral delivery of protein drugs. J Control Release. 2005 Feb 2;102(2):489-507.

  4. Mu L, Feng SS. PLGA/TPGS nanoparticles for controlled release of paclitaxel: effects of the emulsifier and drug loading ratio. Pharm Res. 2003 Nov;20(11):1864-72.

  5. Gao Y, Li LB, Zhai G. Preparation and characterization of Pluronic/TPGS mixed micelles for solubilization of camptothecin. Colloids Surf B Biointerfaces. 2008 Jul 15;64(2):194-9.

Inhibition of the P-glycoprotein (P-gp)

  1. Dintaman JM, Silverman JA. Inhibition of P-glycoprotein by D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS). Pharm Res. 1999 Oct;16(10):1550-6.

  2. Johnson BM, Charman WN, Porter CJ. An in vitro examination of the impact of polyethylene glycol 400, Pluronic P85, and vitamin E d-alpha-tocopheryl polyethylene glycol 1000 succinate on P-glycoprotein efflux and enterocyte-based metabolism in excised rat intestine. AAPS PharmSci. 2002;4(4):E40.

  3. Collnot EM, Baldes C, Wempe MF, Kappl R, Hüttermann J, Hyatt JA, Edgar KJ, Schaefer UF, Lehr CM. Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. Mol Pharm. 2007 May-Jun;4(3):465-74.

Source of Natural Vitamin E

  1. Sokol RJ, Butler-Simon N, Conner C, Heubi JE, Sinatra FR, Suchy FJ, Heyman MB, Perrault J, Rothbaum RJ, Levy J, et al. Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology. 1993 Jun;104(6):1727-35.

  2. Papas K, Kalbfleisch J, Mohon R. Bioavailability of a novel, water-soluble vitamin E formulation in malabsorbing patients. Dig Dis Sci. 2007 Feb;52(2):347-52.

Enhancement of Absorption and Bioavailability

  1. Sokol RJ, Johnson KE, Karrer FM, Narkewicz MR, Smith D, Kam I. Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. Lancet. 1991 Jul 27;338(8761):212-4.

  2. Sokol RJ, Butler-Simon N, Conner C, Heubi JE, Sinatra FR, Suchy FJ, Heyman MB, Perrault J, Rothbaum RJ, Levy J, et al. Multicenter trial of d-alpha-tocopheryl polyethylene glycol 1000 succinate for treatment of vitamin E deficiency in children with chronic cholestasis. Gastroenterology. 1993 Jun;104(6):1727-35.

  3. Chang T, Benet LZ, Hebert MF. The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers. Clin Pharmacol Ther. 1996 Mar;59(3):297-303.

  4. Argao EA, Heubi JE, Hollis BW, Tsang RC. d-Alpha-tocopheryl polyethylene glycol-1000 succinate enhances the absorption of vitamin D in chronic cholestatic liver disease of infancy and childhood. Pediatr Res. 1992 Feb;31(2):146-50.

Delivery and Controlled Release 

  1. Pan J, Feng SS. Targeted delivery of paclitaxel using folate-decorated poly(lactide)-vitamin E TPGS nanoparticles. Biomaterials. 2008 Jun;29(17):2663-72.

  2. Zhang Z, Lee SH, Gan CW, Feng SS. In vitro and in vivo investigation on PLA-TPGS nanoparticles for controlled and sustained small molecule chemotherapy. Pharm Res. 2008 Aug;25(8):1925-35

  3. Mu L, Feng SS. A novel controlled release formulation for the anticancer drug paclitaxel (Taxol): PLGA nanoparticles containing vitamin E TPGS. J Control Release. 2003 Jan 9;86(1):33-48.

  4. Brouwers J, Tack J, Lammert F, Augustijns P. Intraluminal drug and formulation behavior and integration in in vitro permeability estimation: a case study with amprenavir. J Pharm Sci. 2006 Feb;95(2):372-83.

Topical Application

  1. Ahuja M, Dhake AS, Sharma SK, Majumdar DK. Topical ocular delivery of NSAIDs. AAPS J. 2008 Jun;10(2):229-41.

  2. Aydemir O, Celebi S, Yilmaz T, Yekeler H, Kükner AS. Protective effects of vitamin E forms (alpha-tocopherol, gamma-tocopherol and d-alpha-tocopherol polyethylene glycol 1000 succinate) on retinal edema during ischemia-reperfusion injury in the guinea pig retina. Int Ophthalmol. 2004 Oct-Dec;25(5-6):283-9.

  3. Le Bourlais CA, Chevanne F, Turlin B, Acar L, Zia H, Sado PA, Needham TE, Leverge R. Effect of cyclosporine A formulations on bovine corneal absorption: ex-vivo study. J Microencapsul. 1997 Jul-Aug;14(4):457-67.

Animal Nutrition

  1. Dierenfeld, ES; Dolensek, EP. Circulatory levels of vitamin E in captive Asian elephants (Elephas maximus). Zoo Biology, 1988, 7(2): 165-172.

  2. Ullrey, DE, Ku PK, Whetter PA, and Robinson PT. 1989. Black rhinoceros (Diceros bicornis) erythrocyte stability. In Proceedings of the conference of the American Association of Zoo Veterinarians, J. H. Olsen and M. Eisenache (ed.). Greensboro, North Carolina, pp. 19-22.

  3. Papas A, Cambre R, Citino S, Sokol R. Efficacy of absorption of various vitamin E forms by captive elephants and black rhinoceroses. J of Zoo and Wildlife Medicine 199, 22(3): 309-317.

  4. Wooden G, Papas A, Grande A, Utilization of various forms of vitamin E by horses, Twelfth Equine Nutrition and Physiology Society Symposium, Calgary, Alberta, Canada, June 1991.

Safety

  1. Krasavage, W. J. and Terhaar, C. J. d-a-Tocopheryl Polyethylene Glycol 1000 Succinate. Acute Toxicity, Subchronic Feeding, Reproduction, and Teratologic Studies in the Rat. Agriculture and Food Chemistry, 1977, 25 (2): 273-278.

  2. Friman, S., Leandersson, P., Tagesson, C., and Svanvik, J. Biliary Excretion of Different Sized Polyethylene Glycols in the Cat. J Hepatology, 1990, 11: 215-220.