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

• Published in: Biomaterials 2009-09, Vol.30 (27), p.4777-4785
• Main Authors: Guo, Ding-Ding, Xu, Cheng-Xiong, Quan, Ji-Shan, Song, Chung-Kil, Jin, Hua, Kim, Dae-Duk, Choi, Yun-Jaie, Cho, Myung-Haing, Cho, Chong-Su
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Apoptosis - drug effects; Blotting, Western; Cell Cycle - drug effects; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Conjugated linoleic acid; Dentistry; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Hydrogel; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Linoleic Acids, Conjugated - pharmacology; Magnetic Resonance Spectroscopy; Mice; Mice, Nude; Paclitaxel; Paclitaxel - pharmacology; Poloxamer; Poloxamer - pharmacology; Solubility - drug effects; Temperature; Thermosensitive; Time Factors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.05.051

Abstract 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 (CLA)-coupled poloxamer hydrogel for local delivery of paclitaxel (PTX) 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 PTX. The PTX-incorporated CLA-coupled poloxamer thermosensitive hydrogel showed excellent anti-tumor activity in vivo inducing stronger cell cycle arrest and apoptosis in tumor tissue than the PTX-incorporated poloxamer hydrogel. These results were attributed to the synergistic effect of the anti-tumor property of PTX with released CLA from the CLA-coupled poloxamer as the pro-drug and the enhanced solubility of PTX resulting from the micellar property of the CLA-coupled poloxamer. The CLA-coupled poloxamer designed in this study has great potential as an effective injectable carrier of PTX.