| Posted: October 2, 2006 |
Temperature-sensitive nanoparticle boosts drug antitumor activity |
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(Nanowerk News) Using temperature-sensitive, lipid- and polymer-based nanoparticles with a polymer coating, researchers in Korea have created an anticancer drug delivery vehicle that may provide a significant boost to the therapeutic efficacy of anticancer agents, particularly when used in conjunction with hyperthermia. This work is reported in the Journal of Pharmaceutical Sciences ("Hyperthermia-induced antitumor activity of thermosensitive polymer modified temperature-sensitive liposomes").
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Byung Shin, Ph.D., from the Korea Research Institute of Chemical Technology led the research team that developed a temperature-sensitive nanoparticle for delivering doxorubicin to tumors. This particular liposome falls apart and releases its therapeutic payload at temperatures that are slightly elevated from normal body temperature. A polymer coating, made from either poly(ethylene glycol) or poly(N-isopropylacrylamide-co-acrylamide), enhanced the stability of the liposomes in serum by inhibiting the amount of protein that sticks to the nanoparticle. The nanoparticles that the researchers developed contain between 50 - 60% doxorubicin by weight.
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The investigators first studied the release properties of these nanoparticles, demonstrating that they release very little drug at 37°C, normal body temperature. However, at 38°C, drug release soared rapidly as a result of a dramatic change in the stability of the nanoparticles.
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Next, the researchers evaluated tumor response to the doxorubicin-loaded, temperature-sensitive nanoparticles. To assess antitumor activity, the investigators treated mice with human melanoma tumors with saline, plain doxorubicin, or the doxorubicin-nanoparticle formulation, and then measured how much the tumors grew over nine days after a single intravenous injection. The researchers also tracked the effects of a single hyperthermia treatment given one hour after drug injection. The results of this study showed clearly that the drug-nanoparticle formulation in combination with hyperthermia was far superior to any of the other treatments tested.
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