The aim is to improve delivery of the drug rapamycin, which promotes health during ageing in multiple organisms including mammals. The student will develop and characterise the nanocarrier system encapsulating rapamycin using nanospray drying, scanning electron microscopy, laser diffraction particle sizing and in vitro drug release. The viability and proliferation of cells grown with the new rapamycin nanoformulation will be studied. Finally, survival and function during ageing of fruit flies exposed to the nanoformulation will be examined, along with measurement of drug efficacy, and in vivo drug absorption following administration of new rapamycin nanoformulation to aged rodents will be assessed.
Gems D, Partridge L. Genetics of longevity in model organisms: debates and paradigm shifts. Annu Rev Physiol. 2013; 75: 621-644. doi: 10.1146/annurev-physiol-030212-183712.
Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L. Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster. Cell Metab. 2010 January 6; 11(1): 35–46. doi: 10.1016/j.cmet.2009.11.010.
Comas M, Toshkov I, Kuropatwinski KK, Chernova OB, Polinsky A, Blagosklonny MV, Gudkov AV, Antoch MP. New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53-/- mice by delaying carcinogenesis. Aging (Albany NY). 2012 Oct; 4(10):715-722.
Selman C, Partridge L. A double whammy for aging? Rapamycin extends lifespan and inhibits cancer in inbred female mice. Cell Cycle. 2012 Jan 1; 11(1):17-8. doi: 10.4161/cc.11.1.18736.
Hinojosa CA, Mgbemena V, Van Roekel S, Austad SN, Miller RA, Bose S, Orihuela CJ. Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence. Exp Gerontol. 2012 Dec; 47(12):958-65. doi: 10.1016/j.exger.2012.08.013.