title: Trastuzumab-conjugated vitamin E TPGS liposomes for sustained and targeted delivery of docetaxel.
abstract: OBJECTIVE
  In this study, the authors developed D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) liposomes and further conjugated them to trastuzumab for controlled and targeted delivery of docetaxel (DTX) as a model hydrophobic drug.
  
  
  METHODS
  DTX- or coumarin-6-loaded liposomes were prepared by solvent injection method and characterized for size and size distribution, surface charge, surface chemistry and drug encapsulation efficiency and drug release profile. SK-BR-3 cells were employed as an in vitro model for HER2-positive breast cancer and assessed for their cellular uptake and cytotoxicity of the two liposomal formulations. In vivo pharmacokinetics (PK) was investigated in Sprague-Dawley rats.
  
  
  RESULTS
  The IC(50) value was found to be 20.23 ± 1.95, 3.74 ± 0.98, 0.08 ± 0.4 μg/ml for the marketed preparation of DTX, TPGS liposomes and trastuzumab-conjugated TPGS liposomes, respectively after 24 h incubation with SK-BR-3 cells. In vivo PK experiments showed that i.v. administration of trastuzumab-conjugated liposomes achieved 1.9 and 10 times longer half-life, respectively than PEG-coated liposomes and DTX. The area under the curve (AUC) was increased by 3.47- and 1.728-fold, respectively.
  
  
  CONCLUSIONS
  The trastuzumab-conjugated vitamin E TPGS-coated liposomes showed greater potential for sustained and targeted chemotherapy in the treatment of HER2 overexpressing breast cancer.
authors: National University of Singapore, Department of Chemical & Biomolecular Engineering, Block E5-02-11, 4 Engineering Drive 4, Singapore 117576, Singapore.
authors: Anandhkumar
authors: A
authors: Raju
authors: Madaswamy S
authors: MS
authors: Muthu
authors: Si-Shen
authors: SS
authors: Feng
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003374:Coumarins / Q000493:pharmacokinetics / Q000633:toxicity; D000077143:Docetaxel; D004337:Drug Carriers; D006207:Half-Life; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D018613:Microscopy, Confocal; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D043823:Taxoids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity; D013844:Thiazoles / Q000493:pharmacokinetics / Q000633:toxicity; D000068878:Trastuzumab; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D003374:Coumarins; D000077143:Docetaxel; D004337:Drug Carriers; D008081:Liposomes; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; D013844:Thiazoles; D000068878:Trastuzumab; D014810:Vitamin E; C517282:coumarin 6; C014225:tocophersolan