An imaging-driven model for liposomal stability and circulation.
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.
Qin
Shengping
S
Department of Biomedical Engineering, University of California, 451 East Health Sciences Drive, Davis, California 95616, USA.
Seo
Jai Woong
JW
Zhang
Hua
H
Qi
Jinyi
J
Curry
Fitz-Roy E
FR
Ferrara
Katherine W
KW
D000818:Animals; D002199:Capillary Permeability; D016503:Drug Delivery Systems; D015195:Drug Design; D004355:Drug Stability; D005260:Female; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D008081:Liposomes; D051379:Mice; D008954:Models, Biological; D012157:Mononuclear Phagocyte System / Q000000981:diagnostic imaging / Q000378:metabolism; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism; D010599:Pharmacokinetics; D049268:Positron-Emission Tomography
D005456:Fluorescent Dyes; D008081:Liposomes