An imaging-driven model for liposomal stability and circulation

Shengping Qin, Jai Seo, Hua Zhang, Jinyi Qi, Fitz Roy E Curry, Katherine W. Ferrara

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)12-21
Number of pages10
JournalMolecular Pharmaceutics
Volume7
Issue number1
DOIs
StatePublished - Feb 1 2010

Keywords

  • Imaging-driven model
  • Liposomal stability
  • Pharmacokinetic model

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery

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