Preparation and evaluation of teniposide-loaded polymeric micelles for breast cancer therapy

Self-assembled polymeric micelles have been widely applied in anticancer drug delivery systems. Teniposide is a broad spectrum and effective anticancer drug, but its poor water-solubility and adverse effects of commercial formulation (VM-26) restrict its clinical application. In this work, teniposide-loaded polymeric micelles were prepared based on monomethoxy-poly(ethylene glycol)-poly(epsilon-caprolactone-co-D, L-lactide) (MPEG-PCLA) copolymers through a thin-film hydration method to improve the hydrophilic and reduce the systemic toxicity. The prepared teniposide micelles were without any surfactants or additives and monodisperse with a mean particle size of 29.6 +/- 0.3 nm. The drug loading and encapsulation efficiency were 18.53 +/- 0.41% and 92.63 +/- 2.05%, respectively. The encapsulation of teniposide in MPEG-PCLA micelles showed a slow and sustained release behavior of teniposide in vitro and improved the terminal half-life (t(1/2)), the area under the plasma concentration-time curve (AUC) and retention time of teniposide in vivo compared with VM-26. In addition, teniposide micelles also enhanced the cellular uptake by MCF-7 breast cancer cells in vitro and increased the distribution in tumors in vivo. Teniposide micelles showed an excellent safety with a maximum tolerated dose (MTD) of approximately 50 mg teniposide/kg body weight, which was 2.5-fold higher than that of VM-26 ( about 20 mg teniposide/kg body weight). Furthermore, the intravenous application of teniposide micelles effectively suppressed the growth of subcutaneous MCF-7 tumor in vivo and exhibited a stronger anticancer effect than that of VM-26. These results suggested that we have successfully prepared teniposide-loaded MPEG-PCLA micelles with improved safety, hydrophilic and therapeutic efficiency, which are efficient for teniposide delivery. The prepared teniposide micelles may be promising in breast cancer therapy. (C) 2016 Elsevier B.V. All rights reserved.