Papaioannou, Ioannis;
(2006)
Evaluation of colominic acid as a steric stabilisation agent for liposomes.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Conjugation of PEG to liposomes has been shown to prolong their retention in the blood (steric stabilisation). Colominic acid (a-2/8 polysialic acid), a capsular polysaccharide from K1 antigen positive Escherichia coli strains has been proposed as an alternative to PEG. A previous study concluded that colominic acid was able to prolong the circulation time of egg-PC:Cholesterol liposomes, to a small (but significant) extent. In this study, the potential of colominic acid as a steric stabilisation agent was more thoroughly evaluated. Colominic acid of narrowly defined molecular weight was obtained by fractionating the polydisperse commercially available preparations using anion exchange chromatography. Liposomes with saturated lipids were used and the conjugation chemistry was changed to Maleimide chemistry, to obtain a higher degree of grafting. The steric stabilisation capabilities of small (6.2kDa) and large (22.7kDa) colominic acid, conjugated to liposomes in this manner, were investigated by looking at partitioning in PEG-dextran two phase systems, the binding of plasma proteins in vitro and by measuring the half-life of the polysialylated liposomes in vitro. It was found that polysialylated liposomes partitioned in the dextran layer more than control liposomes and their partitioning was not altered by the presence of plasma proteins. Polysialylated liposomes were very effective at blocking the deposition of proteins to the liposome including mouse immunoglobulins and complement C3. Small colominic acid was much more effective than large colominic acid in this respect. In vivo the polysialylated liposomes were cleared faster than control liposomes, but when the mice were preinjected with free colominic acid prior to dosing them with the liposome formulation, the picture was reversed and CA-liposomes circulated longer than control liposomes.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Evaluation of colominic acid as a steric stabilisation agent for liposomes |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Health and environmental sciences; Acid; Colominic; Liposomes; Stabilisation; Steric |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10105139 |
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