Biomedical subjects

Dirk G Lendemans

Publications and source records attributed to Dirk G Lendemans.

3 recordsLinked to original sources

PubMed2006

On the preparation, microscopic investigation and application of ISCOMs.

ISCOM matrices constitute colloidal structures formed from Quillaja saponins, cholesterol and phospholipid. Addition of protein antigens to these matrices leads to the formation of ISCOMs. In this review we report on microscopic investigations of ISCOM matrices and ISCOMs as well as related colloidal structures, such as helices, worm-like micelles, ring-like micelles, and lamellae structures. We briefly outline the immunologic basis for the use of ISCOMs as vaccine delivery systems, and describe the various methods to form ISCOMs. Negative staining transmission electron micrographs of all colloidal structures are presented and described. On the basis of our microscopic investigations, different formation mechanisms of ISCOMS are discussed.

Adjuvants, Immunologic↗

PubMed2005

Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid.

This study describes the formation of cationic, cage-like complexes which have a structure similar to classic anionic ISCOMs. In order to prepare these complexes cholesterol, a major component of classic ISCOM formulations, was substituted with a cationic derivative, 3beta-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-CHOL). Colloidal dispersions with varying compositions of DC-CHOL, phosphatidylcholine, and Quil-A, which is a mixture of anionic triterpene saponins, were prepared by the lipid-film hydration method and characterised by transmission electron microscopy and laser Doppler electrophoresis. The colloidal structures obtained are presented in pseudo-ternary phase diagrams with two buffer systems as the pseudo-component. It was found that the formation of cationic, cage-like particles is highly depending on the formulation buffer. With TRIS buffered saline (TBS) pH 7.4, cage-like particles formed at compositions with high proportions of DC-CHOL and had a strongly positive zeta-potential. These could be purified by differential centrifugation. With phosphate buffered saline pH 7.4, the formation of cage-like particles was much reduced. It was shown that the formation of cage-like particles with a positive charge depended on suitable concentrations of TRIS in the hydration buffer.

Adjuvants, Immunologic↗

PubMed2005

Immuno-stimulating complexes prepared by ethanol injection.

This study describes the formulation of immuno-stimulating complexes (ISCOMs) utilising the ethanol injection technique. Cholesterol and phosphatidylcholine were dissolved in ethanol and the resulting solution was rapidly injected into a stirred, aqueous solution of the triterpene-saponin mixture Quil-A. The reversed experiment was also carried out by adding the aqueous Quil-A solution to a solution of cholesterol/phosphatidylcholine dissolved in ethanol. This was done by either rapid injection or dropwise addition of the aqueous Quil-A solution. The colloidal dispersions obtained by ethanol injection and reversed addition were compared with formulations obtained by the dialysis and lipid-film hydration methods. In a further experiment, the preparation of ISCOMs from liposomes as precursor structures was investigated. Transmission electron microscopy was used to analyse the resulting colloidal dispersions. Samples were also compared with respect to homogeneity of obtained particle species. The ethanol injection technique led to formation of ISCOMs in high numbers within 2 h post formulation. The reversed rapid injection resulted in a similar colloidal dispersion, differing from the former mainly due to the presence of some helical micellar structures. The reversed, dropwise addition led to the formation of helices as the predominant colloidal structure. Of the three previously established methods, only dialysis led to the formation of ISCOMs within 48 h. The lipid-film hydration method and the approach using liposomes as precursor structures did not produce ISCOMs under the conditions and within the time periods investigated. However, it is known that dispersions prepared by the hydration method equilibrate towards ISCOMs after longer storage. Ethanol injection and reversed rapid injection are simple, cost-effective and quick methods to produce ISCOMs.

Chemistry, Pharmaceutical↗