Analysis of the Fate of Systemically Administered Liposomes and Implications for Their Use in Drug Delivery

Peter Bugelski, Richard Kirsh, George Poste, Corazon Bucana, Avraham Raz, Isaiah J. Fidler

Research output: Contribution to journalArticle

267 Scopus citations

Abstract

Functional and ultrastructural studies of liposomes injected i.v. into inbred C57BL/6N mice were performed to determine whether free liposomes can traverse capillaries. In the liver and spleen, organs with discontinuous (sinusoidal) capillaries, ultrastructural and cell fractionation studies revealed that small (300- to 800-A diameter), sonicated, unilamellar liposomes were more efficient in penetrating liver sinusoids to interact with hepatocytes than were large (0.5- to 10-μm) multilamellar liposomes. Ultrastructural studies of the behavior of liposomes in the continuous capillaries of the lungs revealed that circulating phagocytic cells engulf the liposomes in the capillaries. Transcapillary migration of free liposomes was not observed. We conclude that free liposomes are unable to extravasate to reach the alveoli for subsequent engulfment by alveolar macrophages. Instead, liposomes in the lung capillaries are engulfed by circulating blood phagocytes which subsequently migrate to the alveoli to become alveolar macrophages. Experiments on the recruitment of blood monocytes into the lungs subjected to whole- or partial-body X-radiation confirmed that transfer of i.v.-injected liposomes to the alveolar compartment was mediated by blood monocytes. The inability of liposomes to escape from continuous capillaries and their rapid uptake by circulating and fixed phagocytic cells calls into question the feasibility of using liposomes to “target” drugs to cells in extravascular tissues.

Original languageEnglish (US)
Pages (from-to)1412-1422
Number of pages11
JournalCancer Research
Volume42
Issue number4
StatePublished - Apr 1 1982

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Analysis of the Fate of Systemically Administered Liposomes and Implications for Their Use in Drug Delivery'. Together they form a unique fingerprint.

  • Cite this

    Bugelski, P., Kirsh, R., Poste, G., Bucana, C., Raz, A., & Fidler, I. J. (1982). Analysis of the Fate of Systemically Administered Liposomes and Implications for Their Use in Drug Delivery. Cancer Research, 42(4), 1412-1422.