An imaging-driven model for liposomal stability and circulation

Mol Pharm. 2010 Feb 1;7(1):12-21. doi: 10.1021/mp900122j.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Capillary Permeability
  • Drug Delivery Systems*
  • Drug Design
  • Drug Stability
  • Female
  • Fluorescent Dyes
  • In Vitro Techniques
  • Liposomes*
  • Mice
  • Models, Biological*
  • Mononuclear Phagocyte System / diagnostic imaging
  • Mononuclear Phagocyte System / metabolism
  • Nanoparticles
  • Neoplasms, Experimental / blood supply
  • Neoplasms, Experimental / diagnostic imaging
  • Neoplasms, Experimental / metabolism
  • Pharmacokinetics
  • Positron-Emission Tomography

Substances

  • Fluorescent Dyes
  • Liposomes