Vitamin E TPGS coated liposomes enhanced cellular uptake and cytotoxicity of docetaxel in brain cancer cells.

The aim of this work was to develop a drug delivery system of liposomes, which are coated with D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), a PEGylated vitamin E, with docetaxel as a model drug for enhanced treatment of brain tumour in comparison with the nude liposomes as well as with the so-called stealth liposomes, i.e. those coated with polyethylene glycol (PEG), which have been intensive investigated in the literature. Docetaxel or coumarin-6 loaded liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential and drug encapsulation efficiency. C6 glioma cells were employed as an in vitro model to access cellular uptake and cytotoxicity of the drug or coumarin-6 loaded liposomes. The particle size of the PEG or TPGS coated liposomes was ranged between 126 and 191nm. High-resolution field-emission transmission electron microscopy (FETEM) confirmed the coating of TPGS on the liposomes. The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 37.04±1.05, 31.04±0.75, 7.70±0.22, and 5.93±0.57μg/ml for the commercial Taxotere(®), the nude, PEG coated and TPGS coated liposomes, respectively after 24h culture with C6 glioma cells. The TPGS coated liposomes showed great advantages in vitro than the PEG coated liposomes.

[1]  S. Mizrahi,et al.  Use of water-soluble liquid vitamin E to enhance cyclosporine absorption in children after liver transplant. , 1993, Transplantation proceedings.

[2]  S. H. Wu,et al.  Characteristics of D-α-tocopheryl PEG 1000 succinate for applications as an absorption enhancer in drug delivery systems , 1999 .

[3]  M. Bissery,et al.  Experimental antitumor activity of taxotere (RP 56976, NSC 628503), a taxol analogue. , 1991, Cancer research.

[4]  M. S. Muthu,et al.  Multifunctional radionanomedicine: a novel nanoplatform for cancer imaging and therapy. , 2010, Nanomedicine.

[5]  G Gregoriadis,et al.  The carrier potential of liposomes in biology and medicine (second of two parts). , 1976, The New England journal of medicine.

[6]  Ling-chun Chen,et al.  Influence of micelle solubilization by tocopheryl polyethylene glycol succinate (TPGS) on solubility enhancement and percutaneous penetration of estradiol. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[7]  M. S. Muthu,et al.  Targeted nanomedicines: effective treatment modalities for cancer, AIDS and brain disorders. , 2009, Nanomedicine.

[8]  S. Feng,et al.  In vitro and in vivo studies on vitamin E TPGS-emulsified poly(D,L-lactic-co-glycolic acid) nanoparticles for paclitaxel formulation. , 2006, Biomaterials.

[9]  Shu Chien,et al.  Chemotherapeutic engineering: Application and further development of chemical engineering principles for chemotherapy of cancer and other diseases , 2003 .

[10]  G. Gregoriadis.  The Carrier Potential of Liposomes in Biology and Medicine , 1976 .

[11]  H. Yoshioka.  Surface modification of haemoglobin-containing liposomes with polyethylene glycol prevents liposome aggregation in blood plasma. , 1991, Biomaterials.

[12]  T M Allen,et al.  Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. , 1991, Biochimica et biophysica acta.

[13]  S. Feng,et al.  Pharmaceutical stability aspects of nanomedicines. , 2009, Nanomedicine.

[14]  G. Fricker,et al.  Stability of liposomes containing bio-enhancers and tetraether lipids in simulated gastro-intestinal fluids. , 2011, International journal of pharmaceutics.

[15]  G. Zhai,et al.  A liposomal delivery vehicle for the anticancer agent gossypol. , 2008, Anticancer research.

[16]  F. Hartmann,et al.  In vitro evaluation of liposomes containing bio-enhancers for the oral delivery of macromolecules. , 2010, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[17]  S. Feng,et al.  Doxorubicin conjugated to D-alpha-tocopheryl polyethylene glycol succinate and folic acid as a prodrug for targeted chemotherapy. , 2010, Journal of biomedical materials research. Part A.

[18]  Si-Shen Feng,et al.  Formulation of Docetaxel by folic acid-conjugated d-α-tocopheryl polyethylene glycol succinate 2000 (Vitamin E TPGS(2k)) micelles for targeted and synergistic chemotherapy. , 2011, Biomaterials.

[19]  Si-Shen Feng,et al.  The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. , 2006, Biomaterials.

[20]  Ching-Hsien Huang,et al.  Phosphatidylcholine vesicles. Formation and physical characteristics , 1969 .

[21]  Vladimir P Torchilin,et al.  Current trends in liposome research. , 2010, Methods in molecular biology.

[22]  V. Torchilin,et al.  Mixed micelles made of poly(ethylene glycol)-phosphatidylethanolamine conjugate and d-alpha-tocopheryl polyethylene glycol 1000 succinate as pharmaceutical nanocarriers for camptothecin. , 2005, International journal of pharmaceutics.

[23]  Sanjay K. Jain,et al.  Design and development of folate appended liposomes for enhanced delivery of 5-FU to tumor cells , 2007, Journal of drug targeting.

[24]  A. Samad,et al.  Liposomal drug delivery systems: an update review. , 2007, Current drug delivery.

[25]  R. Kappl,et al.  Mechanism of inhibition of P-glycoprotein mediated efflux by vitamin E TPGS: influence on ATPase activity and membrane fluidity. , 2007, Molecular pharmaceutics.

[26]  W. Sawyer,et al.  Reversal of multidrug resistance by surfactants. , 1992, British journal of cancer.

[27]  Si-Shen Feng,et al.  PLGA/TPGS Nanoparticles for Controlled Release of Paclitaxel: Effects of the Emulsifier and Drug Loading Ratio , 2003, Pharmaceutical Research.

[28]  F. Dosio,et al.  Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential , 2006, International journal of nanomedicine.

[29]  M. Carafa,et al.  Potential dopamine prodrug-loaded liposomes: preparation, characterization, and in vitro stability studies , 2010, Journal of liposome research.

[30]  M. S. Muthu,et al.  Studies on biodegradable polymeric nanoparticles of risperidone: in vitro and in vivo evaluation. , 2008, Nanomedicine.

[31]  S. Feng,et al.  Nanopharmacology of liposomes developed for cancer therapy. , 2010, Nanomedicine.

[32]  Robert J. Lee,et al.  A folate receptor-targeted liposomal formulation for paclitaxel. , 2006, International journal of pharmaceutics.

[33]  Si-Shen Feng,et al.  Fabrication and characterizations of a novel drug delivery device liposomes-in-microsphere (LIM). , 2004, Biomaterials.

[34]  H. Devalapally,et al.  Role of nanotechnology in pharmaceutical product development. , 2007, Journal of pharmaceutical sciences.

[35]  R. C. Dutta.  Drug carriers in pharmaceutical design: promises and progress. , 2007, Current pharmaceutical design.

[36]  S. Feng,et al.  Doxorubicin conjugated to D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS): conjugation chemistry, characterization, in vitro and in vivo evaluation. , 2008, Biomaterials.

[37]  P. Vrignaud,et al.  Preclinical evaluation of docetaxel (Taxotere). , 1995, Seminars in oncology.

[38]  M. S. Muthu,et al.  PLGA nanoparticle formulations of risperidone: preparation and neuropharmacological evaluation. , 2009, Nanomedicine : nanotechnology, biology, and medicine.

[39]  L. Benet,et al.  The effect of water‐soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers , 1996, Clinical pharmacology and therapeutics.

[40]  J. Silverman,et al.  Inhibition of P-Glycoprotein by D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) , 1999, Pharmaceutical Research.

[41]  J. Hobbs.  Medical application of liposomes: Kunio Yagi (editor) Japan Scientific Societies Press, Tokyo/Japan 1986 Karger, London, UK, 201 pp., £56.10 , 1987 .

[42]  Kazuo Maruyama,et al.  Intracellular targeting delivery of liposomal drugs to solid tumors based on EPR effects. , 2011, Advanced drug delivery reviews.

[43]  S. Feng,et al.  Vitamin E TPGS used as emulsifier in the solvent evaporation/extraction technique for fabrication of polymeric nanospheres for controlled release of paclitaxel (Taxol). , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[44]  M. Varma,et al.  Enhanced oral paclitaxel absorption with vitamin E-TPGS: effect on solubility and permeability in vitro, in situ and in vivo. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.