title: An imaging-driven model for liposomal stability and circulation.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, University of California, 451 East Health Sciences Drive, Davis, California 95616, USA.
authors.forename: Shengping
authors.initials: S
authors.lastname: Qin
authors.forename: Jai Woong
authors.initials: JW
authors.lastname: Seo
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Jinyi
authors.initials: J
authors.lastname: Qi
authors.forename: Fitz-Roy E
authors.initials: FR
authors.lastname: Curry
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Ferrara
mesh_terms: 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
chemical_list: D005456:Fluorescent Dyes; D008081:Liposomes