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 journalArticle

32 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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    Qin, S., Seo, J., Zhang, H., Qi, J., Curry, F. R. E., & Ferrara, K. W. (2010). An imaging-driven model for liposomal stability and circulation. Molecular Pharmaceutics, 7(1), 12-21. https://doi.org/10.1021/mp900122j