Rapamycin in lipoproteins for enhanced delivery

While rapamycin was discovered as a fungicide in 1975, it is now famous for its ability to suppresses mammalian cell aging and to extend lifespan in mice. Rapamycin is an oral immunomodulatory agent approved to prevent rejection in human organ transplantation. It also exerts an antitumor activity as well as an anti-restenosis activity, when used in drugeluting stents. In addition, rapamycin has neuroprotective effects in traumatic brain injury models, with increased neuron survival and recovery of brain functions. Nevertheless, there has been a practical limitation in performing physiologic studies with rapamycin, because rapamycin has very poor water solubility and bioavailability. To maximize the research and clinical application of rapamycin, it is advantageous to dissolve rapamycin in a physiologic and isotonic solution. To overcome this limitation (poor water solubility), we solubilized rapamycin in isotonic buffer using reconstituted highdensity lipoprotein containing V156KapoA-I (V156K-rHDL). Apolipoprotein (apo) A-I is a principal protein component of HDL and is known to perform a beneficial role in the reverse cholesterol transport pathway through its antioxidant and antiinflammatory activities. HDL have atheroprotective effects with potent antioxidant, antiinflammatory, anti-diabetic activities. Recently, we showed that rHDL containing V156K-apoA-I, had a potent antioxidant activity and was more resistant to glycation, with more enhanced tissue regeneration activity as a HDLtherapy. More resistance to glycation is advantageous to develop a protein-based drug for both anti-atherosclerotic and anti-diabetic agents. These results suggest Rapamycin in lipoproteins for enhanced delivery