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Related Experiment Videos

Transmembrane gradient driven phase transitions within vesicles: lessons for drug delivery

D D Lasic1, B Ceh, M C Stuart

  • 1Liposome Technology Inc., Menlo Park, CA, USA.

Biochimica Et Biophysica Acta
|November 1, 1995
PubMed
Summary

Phase transitions in vesicles are key for drug delivery. Doxorubicin shows excellent retention, while ciprofloxacin has poor retention due to its properties and precipitation form.

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Area of Science:

  • Biochemistry
  • Materials Science
  • Pharmacology

Background:

  • Phase transitions in closed vesicles are crucial for various applications, including drug delivery.
  • Lipid bilayer membranes control the transport of ions and molecules.
  • Efficient liposomal therapeutics require high drug loading and low leakage rates.

Purpose of the Study:

  • To investigate efficient drug encapsulation via intraliposomal precipitation.
  • To characterize the state of encapsulated drugs within liposomes.
  • To validate a theoretical model for membrane-permeable species based on chemical potential equilibration.

Main Methods:

  • Intraliposomal precipitation for drug encapsulation.
  • Characterization of encapsulated drug states.

Related Experiment Videos

  • Comparison of experimental data with a theoretical model.
  • High-resolution cryo-electron microscopy (cryoEM) for visualizing precipitate structures.

    • Main Results:

    • High drug loading efficiencies were achieved through intraliposomal precipitation.
    • A theoretical model based on chemical potential equilibration showed good agreement with experimental data.
    • Anticancer drug doxorubicin precipitated as fibers, exhibiting low solubility and minimal leakage.
    • Antibiotic ciprofloxacin precipitated as globules, showing higher solubility and significant in vitro/in vivo leakage.

    Conclusions:

    • Intraliposomal precipitation is an effective method for high drug loading.
    • Drug retention in liposomes depends on precipitation form, solubility, and membrane permeability.
    • Doxorubicin's fibrous precipitate ensures long-term retention, crucial for effective therapies.
    • Ciprofloxacin's globular precipitate and membrane permeability lead to poor retention, limiting its therapeutic efficacy.