TY - JOUR
T1 - Liposomal Formulation of Retinoids Designed for Enzyme Triggered Release
AU - Pedersen, Palle Jacob
AU - Adolph, Sidsel Kramshøj
AU - Subramanian, Arun Kumar
AU - Arouri, A.
AU - Andresen, Thomas Lars
AU - Mouritsen, O.G.
AU - Madsen, Robert
AU - Madsen, M.W.
AU - Peters, Günther H.J.
AU - Clausen, Mads Hartvig
PY - 2010
Y1 - 2010
N2 - The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.
AB - The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A(2) IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A(2), the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 mu M toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A(2), while no significant cell death was observed in the absence of the enzyme.
U2 - 10.1021/jm100190c
DO - 10.1021/jm100190c
M3 - Journal article
SN - 0022-2623
VL - 53
SP - 3782
EP - 3792
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 9
ER -
