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 (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.
Guo
Ding-Ding
DD
Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, South Korea.
Xu
Cheng-Xiong
CX
Quan
Ji-Shan
JS
Song
Chung-Kil
CK
Jin
Hua
H
Kim
Dae-Duk
DD
Choi
Yun-Jaie
YJ
Cho
Myung-Haing
MH
Cho
Chong-Su
CS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology*; D020442:Poloxamer / Q000494:pharmacology*; D012995:Solubility / Q000187:drug effects; D013696:Temperature; D013997:Time Factors
D018797:Cell Cycle Proteins; D044243:Linoleic Acids, Conjugated; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D017239:Paclitaxel