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

Received 25 January 2011; accepted 4 November 2011. published online 18 November 2011.
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Abstract 

The purpose of this study was to develop polymeric nanoscale drug-delivery system (nano-DDS) for paclitaxel (PTX) from poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-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.

Graphical Abstract 

Flower-like PTX-loaded polymeric micelles from PCL4000-PEG8000-PCL4000 were successfully prepared by thin film method. The obtained micelles exhibited apparent core-shell morphology with satisfactory size (93 nm), which were favorable for intravenous injection. In vivo anti-tumor study showed that the PTX-loaded polymeric micelles could significantly inhibit EMT6 breast tumor growth and reduce the toxicity of PTX. The prepared PTX-loaded polymeric micelles have the potential to be developed as an effective anticancer nano-scale drug delivery system for cancer chemotherapy.

Key words: Polymeric micelles, PCL-PEG-PCL, Paclitaxel, Anti-tumoral activity, Pharmacokinetics

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 Conflict of interest: The authors report no conflict of interest.

 This work was supported by Natural Science Foundation of China (No. 51103180, No. 50873114 and No. 50903093) and Tianjin Natural Science Foundation (No. 11JCYBJC02400 and No. 10JCYBJC01700).

PII: S1549-9634(11)00525-9

doi:10.1016/j.nano.2011.11.005

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