Transferrin receptor targeted PLA-TPGS micelles improved efficacy and safety in docetaxel delivery

Abstract

The aim of this work was to develop targeted polymeric micelles of poly-lactic acid-d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS), which are assembled along with d-alpha-tocopheryl polyethylene glycol 1000 succinate-transferrin conjugate (TPGS-Tf), and loaded docetaxel (DTX) as a model drug for enhanced treatment of lung cancer in comparison to non-targeted polymeric micelles and DTX injection (Docel™). A549 human lung cancer cells were employed as an in vitro model to access cytotoxicity study of the DTX loaded polymeric micelles. The safety of DTX formulations were studied by the measurement of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total protein levels in bronchoalveolar lavage (BAL) fluid of rats after the treatments. The IC50 values demonstrated that the non-targeted and transferrin receptor targeted polymeric micelles could be 7 and 70 folds more effective than Docel™ after 24 h treatment with the A549 cells. Results suggested that transferrin receptor targeted polymeric micelles have showed better efficacy and safety than the non-targeted polymeric micelles and Docel™. © 2015 Elsevier B.V.