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In vivo temperature-sensitive drug release system trigged by cooling using low-melting-point microcrystalline wax

Matsumoto, Kohei, Kimura, Shin-ichiro, Itai, Shigeru, Kondo, Hiromu, Iwao, Yasunori
Journal of controlled release 2019 v.303 pp. 281-288
body temperature, cooling, drugs, rats
Temperature-sensitive formulations are attractive controlled-release formulations, which release an incorporated drug by changes in body temperature induced by external temperature stimulation. Recently, it has been reported that wax matrix (WM) particles composed of a low-melting-point microcrystalline wax (MCW) released only a small amount of the drug at 37 °C, whereas faster drug release occurred at 25 °C. In this study, temperature-sensitive formulations composed of low-melting-point MCW that release drugs triggered by cooling, rather than heating, were developed. In an in vitro dissolution test in which the test medium was repeatedly cooled from 37 to 25 °C, control of the promotion and suppression of drug release was achieved. The drug concentration in the plasma of rats administered the particles was significantly increased by cooling compared with non-cooling, indicating that the drug release from the particles was promoted by cooling both in vitro and in vivo. Therefore, particles composed of low-melting-point MCW should be useful for the development of cooling-triggered, temperature-sensitive formulations.