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Related Experiment Videos

Elastase activated liposomal delivery to nucleated cells.

C C Pak1, R K Erukulla, P L Ahl

  • 1The Liposome Company, 1 Research Way, Princeton, NJ 08540, USA.

Biochimica Et Biophysica Acta
|July 17, 1999
PubMed
Summary

Enzyme-cleavable peptides linked to liposomes enable targeted drug delivery. This system, activated by elastase, enhances lipid mixing and delivery of contents to specific cells, improving therapeutic potential.

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Area of Science:

  • Biotechnology
  • Drug Delivery Systems
  • Biochemistry

Background:

  • Liposomes are versatile drug carriers, but targeted delivery remains a challenge.
  • Enzyme-mediated activation of liposomes offers a strategy for triggered release.
  • Previous work demonstrated elastase-sensitive peptide-lipids for liposome fusion.

Purpose of the Study:

  • To develop and optimize an enzyme-responsive liposome system for targeted delivery.
  • To achieve substrate cleavage at physiological elastase levels.
  • To demonstrate triggered delivery of encapsulated substances to living cells.

Main Methods:

  • Synthesis of a novel elastase-sensitive peptide-lipid (MeO-suc-AAPV-DOPE).
  • Co-formulation of the peptide-lipid with a cationic lipid (DODAP).

Related Experiment Videos

  • Incubation of liposomes with human leukemic (HL60) and endothelial (ECV304) cells in the presence or absence of elastase.
  • Assessment of liposome binding, lipid mixing, and cargo delivery (dextrans, calcein).

    • Main Results:

    • The new peptide-lipid showed enhanced sensitivity and selectivity for elastase.
    • Elastase-treated liposomes exhibited pH-dependent binding, lipid mixing, and dextran delivery to HL60 cells.
    • Enzymatic activity of elastase was confirmed as necessary for activation.
    • Activated liposomes successfully delivered encapsulated calcein into ECV304 cell cytoplasm.

    Conclusions:

    • Enzyme substrate peptides conjugated to fusogenic lipids can trigger specific liposome delivery.
    • This approach holds promise for targeted drug delivery to cells expressing specific enzymes.
    • The system demonstrates potential for enhanced therapeutic efficacy and reduced off-target effects.