Aspects of cytotoxic drug penetration

The aims of this thesis are summarised as follows: a) Investigation of the cellular pharmacokinetics of adriamycin accumulation in human lung tumour rnonolayers and its relationship to cytotoxicity. b) Comparison of the rate, degree of uptake and cellular localisation of lipophilic derivatives of adriamycin in monolayer systems. c) Comparison of adriamycin and lipophilic anthracycline derivatives in multicellular spheroids with regard to differential penetration and cytotoxicity. d) Identification of putative adriamycin penetration enhancing agents, such as membrane permeabilisers, in monolayer and their further study in spheroid culture systems. e) Investigation of the distibution and penetration of adriamycin in solid tumour systems. f) Comparison of the pharmacokinetics and cytotoxicity of adriamycin and adriamycin encapsulated in slow release surfactant vesicles (niosomes) in nude mice bearing human lung tumour xenografts