Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278496
Title: An examination of the effect of surface modifications on the physicochemical and biological properties of non-ionic surfactant vesicles
Author: Cable, Colin
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 1990
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Abstract:
The physicochemical properties of non-ionic surfactant vesicles (NSV's), formed from the non-ionic surfactants I. II and IV (monoalkyl and dialkyl polyglyceryl ethers), were examined. The effects of incorporating polyoxyethylene cholesteryl ethers and charged molecules into the vesicular bilayer on these properties were examined and their potential as drug delivery vehicles for doxorubicin (DOX) investigated. The size and aqueous entrapment volume of vesicles were related to the preparation method, although charged molecules or increasing the hydrophilicity did affect both parameters. The vesicular surface charge, due to adsorbed hydroxyl ions or incorporated charged molecules, was reduced as the polyoxyethylene chain length of incorporated cholesteryl ethers was increased. The vesicular charge of vesicles containing cholesteryl polyoxyethylene(24)ether (SOL24) was unaffected by the encapsulation of DOX but encapsulation of the drug in positively charged vesicles markedly affected the charge against pH profile. Increasing the vesicular cholesterol content reduced the enthalpy of the phase transition, ultimately abolishing the peak between 33-50mol% cholesterol, while the peak shape was altered by the addition of charged molecules. Vesicular aggregation was induced by NaCl, although incorporation of charged molecules or SOL24 to the vesicular bilayer prevented this flocculation. DOX release from drug loaded vesicles was markedly reduced by the inclusion of cholesterol or stearylamine (SA) in the bilayer, while the incorporation of SOL24 produced a slight reduction. Empty vesicles containing SOL24 and SA molecules interacted with DOX molecules; SOL24 produced an immediate and reversible interaction and SA produced a delayed but apparently irreversible interaction. Administration of DOX loaded, SOL24 containing vesicles to mice reduced the peak cardiac concentration and produced a higher terminal plasma concentration compared with free drug. The co-administration of free drug with empty vesicles increased drug concentrations in the heart and kidney. The intravenous injection of DOX loaded. SA containing vesicles into mice bearing a subcutaneously implanted ROS tumour gave inconclusive results due to analytical problems, although the injection of empty vesicles with free drug behaved similarly to free drug alone. Drug loaded vesicles were much less effective at retarding tumour growth than either of the free drug containing samples despite fluorescence photomicrographs showing the majority of the vesicles residing within the tumour vasculature.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.278496  DOI: Not available
Keywords: Pharmacology & pharmacy & pharmaceutical chemistry Pharmacology Biochemistry
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