Synthesis of cationic derivatives of Quil A and the preparation of cationic immune-stimulating complexes (ISCOMs)

Pham, Hoang L., Ross, Benjamin P., McGeary, Ross P., Shaw, P. Nicholas and Davies, Nigel M. (2009) Synthesis of cationic derivatives of Quil A and the preparation of cationic immune-stimulating complexes (ISCOMs). International Journal of Pharmaceutics, 376 1-2: 123-133. doi:10.1016/j.ijpharm.2009.04.011


Author Pham, Hoang L.
Ross, Benjamin P.
McGeary, Ross P.
Shaw, P. Nicholas
Davies, Nigel M.
Title Synthesis of cationic derivatives of Quil A and the preparation of cationic immune-stimulating complexes (ISCOMs)
Journal name International Journal of Pharmaceutics   Check publisher's open access policy
ISSN 0378-5173
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1016/j.ijpharm.2009.04.011
Open Access Status
Volume 376
Issue 1-2
Start page 123
End page 133
Total pages 11
Editor A. T. Florence
Place of publication Netherlands
Publisher Elsevier BV
Language eng
Subject C1
111504 Pharmaceutical Sciences
0304 Medicinal and Biomolecular Chemistry
970111 Expanding Knowledge in the Medical and Health Sciences
970103 Expanding Knowledge in the Chemical Sciences
Abstract The aim of the study was to prepare cationic ISCOMs using cationic derivatives of the saponin Quil A. The polyamines ethylenediamine, spermidine and spermine were conjugated with the glucuronic acid moiety of Quil A. The aqueous solubility of the derivatives increased with decreasing pH, and the pKa values were between 6 and 7. The CMCs of the ionised derivatives were around 0.5–1.0 mg/mL. Using the method of hydration of freeze-dried monophase systems, the interaction of each of the Quil A derivatives with phosphatidylcholine and cholesterol, at a mass ratio of 4:4:2 and a pH of 3 and 7.4, was investigated. A few ISCOM-like structures were present in the systems prepared at pH 7.4, hence the ternary system of Quil A spermine derivative, phosphatidylcholine and cholesterol was further investigated at pH 7.4 using a variety of mass ratios. A relatively high number of cationic ISCOM-like structures were observed at the mass ratio of 6:2:2. These ISCOM-like structures were less homogeneous and more irregular in shape than ISCOMs prepared from unmodified Quil A. Colloidal particles with positive zeta potential were produced and may find application in the delivery of nucleic acids or anionic proteins.
Keyword ISCOMs
Quil A derivatives
Quil A
Immune-stimulating Complexes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
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Created: Sat, 20 Jun 2009, 02:08:32 EST by Charna Kovacevic on behalf of School of Pharmacy