Paclitaxel-loaded polymeric micelles based on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) triblock copolymers: in vitro and in vivo evaluation

The purpose of this study was to develop polymeric nanoscale drug-delivery system (nano-DDS) for paclitaxel (PTX) from poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) copolymers, intended to be intravenously administered, able to improve the therapeutic efficacy of the drug and devoid of the adverse effects of Cremophor EL. Both of the PTX-loaded polymeric micelles and polymersomes were successfully prepared from PCEC copolymers. The obtained PTX-loaded micelles exhibited core-shell morphology with satisfactory size (93 nm), and were favorable for intravenous injection. In vitro cytotoxicity demonstrated that the cytotoxic effect of PTX-loaded micelles was lower than that of Taxol (Bristol-Myers Squibb, Princeton, New Jersey). Pharmacokinetic results indicated that the PTX-loaded micelles had longer systemic circulation time and slower plasma elimination rate than those of Taxol. Furthermore, PTX-loaded micelles showed greater tumor growth-inhibition effect in vivo on EMT6 breast tumor, in comparison with Taxol. Therefore, the prepared polymeric micelles might be potential nano-DDS for PTX delivery in cancer chemotherapy. From the Clinical Editor: In this paper, a paclitaxel-loaded polymeric micelle system is demonstrated to provide optimized intravenous delivery method of this anti-cancer agent. While the study is early preclinical, this approach may have the potential to eventually be studied in clinical trials as well. (C) 2012 Elsevier Inc. All rights reserved.