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Studies on size reduction of liposomes and their stabilization

Zadi, Brahim; (2000) Studies on size reduction of liposomes and their stabilization. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The aim of this work was to obtain a better insight into the requirement for size reduction for liposomal formulations, their stability in terms of retention of encapsulated compounds and size conservation upon drying and rehydration. Chapter three is devoted to the investigation of the microfluidisation of liposomes according to planned experiments. This made possible the quantification of the effect of some specific parameters, the prediction and the optimization of the outcome of microfluidisation (retention of the encapsulated compound upon optimal size reduction). The size reduction was very substantial but always correlated with a loss of the encapsulated compound. Problems associated with liposomal suspensions remained unsolved. In chapter four the spray-drying of liposomes was investigated aiming at providing some solutions with a view to improve the liposomal stability. The morphology of the dried product (consisting of mixtures of liposomes and carbohydrate) were studied along with any occurring oxidative damage. The nature and the amount of carbohydrate used were varied in order to study their effect on the liposome characteristics on rehydration. Liposomal size reduction prior to spray-drying was found to be a key factor in improving the retention of the encapsulated compound upon rehydration. In chapter five the release of the encapsulated drug from spray- dried liposomes upon incubation with lung surfactant and Triton X-100 is studied. The emphasis was laid on the effect of the temperature of incubation as well as on the liposomal size reduction. Liposomes made out of lipids exhibiting a high Tc exhibited a better stability and a slower release of the marker. The size reduction of liposomes prior to drying appeared to be a decisive factor in minimising drug leakage upon drying and rehydration. Based on these finding, a novel method (Chapter 6) was developed in which a substantial amount of drug could be loaded in relatively small liposomes upon drying and rehydration. Defined amounts of sucrose present with the drug to be encapsulated mixed with the small unilamellar liposomes (SUV) followed by freeze-drying allows the control of the fusion/aggregation processes and the production of small drug-loaded liposomes on subsequent rehydration. The product obtained is dry and it can be stored as such, thus avoiding problems of drug leakage, size growth and lipid degradation. The product can be reconstituted easily, just before administration and does not require any further treatment for size reduction. Parameters such as the molarity of the sucrose solution, the lipid composition and the temperature of rehydration were studied. A comparison of the results obtained by this method and of those obtained when the extrusion technique was employed was carried out. Finally, the overall results obtained in this thesis were discussed in the final chapter (chapter 7). It contains some suggestions and remarks concerning future work.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Studies on size reduction of liposomes and their stabilization
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10113556
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