New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53 −/− mice by delaying carcinogenesis

摘要: The nutrient-sensing mTOR (mammalian Target of Rapamycin) pathway regulates cellular metabolism, growth functions, and proliferation is involved in age-related diseases including cancer, type 2 diabetes, neurodegeneration cardiovascular disease. inhibition by rapamycin, or calorie restriction, has been shown to extend lifespan delays tumorigenesis several experimental models suggesting that rapamycin may be used for cancer prevention. This requires continuous long-term treatment making oral formulations the preferred choice administration route. However, itself very poor water solubility low absorption rate. Here we describe pharmacokinetic biological properties novel nanoformulated micelles Rapatar. Micelles Rapatar were rationally designed increase facilitate enhance its absorption. As a result, bioavailability was significantly increased (up 12%) compared unformulated which concentration blood following remained below level detection. We also demonstrated new formulation does not induce toxicity during lifetime administration. Most importantly, extended mean 30% delayed tumor development highly tumor-prone p53−/− mice. Our data demonstrate soluble represent safe, convenient efficient form suitable considered