Synergistic anti-tumor activity of paclitaxel-incorporated conjugated linoleic acid-coupled poloxamer thermosensitive hydrogel in vitro and in vivo

Local delivery of anti-tumor drugs provides a high local concentration and decreases the incidence of side effects commonly observed with systemic therapy. Hydrogel systems are commonly used as a local drug delivery system. In this study, we prepared a novel thermosensitive conjugated linoleic acid (CIA)coupled poloxamer hydrogel for local delivery of paclitaxel (M) to gain the benefits of the pro-drug activity of the CLA-coupled poloxamer and enhanced PTX solubility due to the micellar property of the CLA-coupled poloxamer. To evaluate the anti-tumor activity of the PTX-incorporated CLA-coupled poloxamer hydrogel in vivo, formulations were injected subcutaneously into tumor-bearing mice. Cell cycle and apoptosis markers were examined to determine the mechanism of the anti-tumor activity of M. The MX-incorporated CLA-coupled poloxamer thermosensitive hydrogel showed excellent antitumor activity in vivo inducing stronger cell cycle arrest and apoptosis in tumor tissue than the Mincorporated poloxamer hydrogel. These results were attributed to the synergistic effect of the antitumor property of M with released CIA from the CIA-coupled poloxamer as the pro-drug and the enhanced solubility of PTX resulting from the micellar property of the CLA-coupled poloxamer. The CIA-coupled poloxamer designed in this study has great potential as an effective injectable carrier of M. (C) 2009 Elsevier Ltd. All rights reserved.