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. 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. 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. The trastuzumab-conjugated vitamin E TPGS-coated liposomes showed greater potential for sustained and targeted chemotherapy in the treatment of HER2 overexpressing breast cancer.