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The application of liposomes for solubilisation of hydrophobic drugs

Leigh, Mathew Louis Steven; (1997) The application of liposomes for solubilisation of hydrophobic drugs. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The application of liposomes for the solubilisation of lipophilic hydrophobes for intravenous administration has been investigated. The lipid composition of four commercially available phospholipids extracted from soya bean and egg sources were studied. The particle size of liposome dispersions generated from pro-liposomes made from these four phospholipids was determined using a variety of sizing techniques. Various factors potentially affecting the particle size such as the degree of agitation, lipid composition and hydration of the liposome were studied. The size distribution of the dispersions without drug were compared to a commercially available intravenous emulsion. The stability of three placebo anhydrous lipid formulations was examined under accelerated conditions. The harsh conditions induced extensive browning in the soya phospholipid and egg phospholipid samples. Oxidative changes were most pronounced in the soya phosphatidylcholine formulations. Long term stability studies at 40 °C, 20 °C and 4 °C were also carried out on a specific soya phospholipid blend proliposome formulation. In this particular study, the oxidative status of the lipid remained essentially unchanged throughout the test period. The model hydrophobe selected for these studies was the immunosupressant cyclosporin A (cyA). Association of cyA was found to be dependent upon a careful balance of the pro-liposome components. Furthermore, association was further improved by hydrating the pro-liposome with an appropriate amount of water. Freeze drying was investigated as a possible alternative presentation of cyA liposomes. Studies on drug-free dispersions revealed that successful freeze drying was reliant upon a variety of factors such as lipid composition, careful selection of stabilisers and freezing. The particle size of all liposome dispersions examined was larger than the original dispersion prior to lyophilisation. However, the association of cyA was unaffected by freeze drying. After rehydration, cyA remained associated with all the liposome dispersions tested-even those which had fused/aggregated to a large extent.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The application of liposomes for solubilisation of hydrophobic drugs
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; Drugs; Hydrophobic; Liposomes; Solubilisation
URI: https://discovery.ucl.ac.uk/id/eprint/10105304
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