An Imaging-Driven Model for Liposomal Stability and Circulation

作者：Qin Shengping; Seo Jai Woong; Zhang Hua; Qi Jinyi; Curry Fitz Roy E; Ferrara Katherine W^*

来源：Molecular Pharmaceutics, 2010, 7(1): 12-21.

DOI：10.1021/mp900122j

• Pharmacokinetic model
• imaging-driven model
• liposomal stability

Simultaneous labeling of the drug compartment and shell of delivery vehicles with optical and positron emission tomography (PET) probes is developed and employed to inform a hybrid physiologically based pharmacokinetic model. Based on time-dependent estimates of the concentration of these tracers within the blood pool, reticuloendothelial system (RES) and tumor interstitium, we compare the stability and circulation of long-circulating and temperature-sensitive liposomes. We find that rates of transport to the RES for long-circulating and temperature-sensitive particles are 0.046 and 0.19 h(-1), respectively. Without the application of exogenous heat, the rates of release from the long-circulating and temperature-sensitive particles circulating within the blood pool are 0.003 and 0.2 h(-1), respectively. Prolonged lifetime in circulation and slow drug release from liposomes result in a significantly greater drug area under the curve for the long-circulating particles. Future studies will couple these intrinsic parameters with exogenous heat-based release. Finally, we develop a transport constant for the transport of liposomes from the blood pool to the tumor interstitium, which is on the order of 0.01 h(-1) for the Met-1 tumor system.

• 出版日期2010-2