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Preparation of immuno-stimulating complexes (ISCOMs) by ether injection.

H L Pham1, P N Shaw, N M Davies

  • 1School of Pharmacy, The University of Queensland, St. Lucia, Brisbane 4072, QLD, Australia.

International Journal of Pharmaceutics
|January 18, 2006
PubMed
Summary

Ether injection successfully prepared ImmunoStimulating Complexes (ISCOMs) using a continuous, scalable method. Optimal conditions yielded homogeneous ISCOMs, while variations produced heterogeneous mixtures with other structures.

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Area of Science:

  • Biotechnology
  • Nanotechnology
  • Immunology

Background:

  • Liposome preparation commonly uses solvent dispersion.
  • ImmunoStimulating Complexes (ISCOMs) are potent vaccine adjuvants.
  • A continuous, scalable ISCOM preparation method is needed.

Purpose of the Study:

  • To develop a novel, continuous, and scalable method for ISCOM preparation using ether injection.
  • To investigate critical parameters influencing ISCOM formation and homogeneity.

Main Methods:

  • Solvent dispersion (ether injection) of phosphatidylcholine (PC) and cholesterol (Chol) into an aqueous Quil A solution.
  • Systematic variation of PC:Quil A:Chol ratio, injection rate, lipid mass, and buffer conditions.
  • Characterization using transmission electron microscopy, photon correlation spectroscopy, and sucrose ultracentrifugation.

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Main Results:

  • ISCOMs were successfully produced via ether injection.
  • Homogeneous ISCOM formation required specific conditions: PC:Quil A:Chol ratio of 5:3:2, 20 mg total lipid mass, 6 mg/4 ml Quil A in 0.01 M phosphate buffer, and 0.2 ml/min injection rate.
  • Deviations from optimal conditions led to heterogeneous preparations with co-existing colloidal structures.

Conclusions:

  • Ether injection is a viable method for ISCOM preparation.
  • Precise control over formulation and process parameters is crucial for achieving homogeneous ISCOMs.
  • This method offers potential for scalable ISCOM production.