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Related Experiment Videos

Species difference in correlation between in vivo/in vitro liposome-complement interactions.

T M Huong1, T Ishida, H Harashima

  • 1Department of Pharmacokinetics and Pharmaceutics, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Japan.

Biological & Pharmaceutical Bulletin
|April 18, 2001
PubMed
Summary

This study found that liposomes activated the complement system in rats but not guinea pigs in vivo. In vitro tests showed complement activation in rats but not guinea pigs, highlighting a discrepancy in liposome-complement interactions.

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Area of Science:

  • Liposome-complement interactions
  • Immunology
  • Drug delivery systems

Background:

  • Liposomes are widely used in drug delivery.
  • Understanding liposome-complement interactions is crucial for predicting in vivo behavior.
  • Hydrogenated egg phosphatidylcholine (HEPC)-based liposomes are a common formulation.

Purpose of the Study:

  • To investigate the correlation between in vitro and in vivo liposome-complement interactions.
  • To determine complement component 3 (C3) fragment association in vivo and complement-dependent destabilization in vitro.
  • To assess the predictive value of in vitro assays for in vivo liposome behavior.

Main Methods:

  • Liposome-complement interaction was assessed by detecting C3 fragments on HEPC-based liposomes in rats and guinea pigs.

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  • Complement activation was evaluated in vitro by measuring complement-dependent liposome destabilization in rat and guinea pig serum.
  • Liposomes were pretreated with K76COOH (K76), a complement inactivating agent, to confirm complement involvement.

    • Main Results:

    • C3 fragments were detected on liposomes in both rats and guinea pigs in vivo, indicating complement activation.
    • Pretreatment with K76 reduced C3 fragment binding, confirming complement system activation.
    • Significant complement-dependent liposome destabilization occurred in rat serum (in vitro), but not in guinea pig serum (in vitro).

    Conclusions:

    • In vitro complement activation assays did not align with in vivo observations in guinea pigs.
    • Liposomes activated the complement system in rats both in vitro and in vivo.
    • Discrepancies in liposome-complement interactions necessitate further research for accurate prediction of in vivo liposome behavior.