Summary Niosomes are multilamellar vesicles formed from nonionic surfactants of the alkyl or dialkyl polyglycerol ether class and cholesterol. Adriamycin has been trapped within vesicles prepared from a monoalkyl triglycerol ether and its activity compared with adriamycin solution in human lung tumour cells grown in monolayer and spheroid culture and in tumour xenografted nude mice. The activity of the encapsulated adriamycin in vitro is maintained with similar clonogenic survival curves following treatment of monolayers and identical growth delays following spheroid exposure. The pharmacokinetics of adriamycin are altered in vivo in human lung tumour-bearing nude mice, when it is administered in niosomal form. There is prolonged release of drug from the plasma compartment with significantly lower peak levels; lower peak cardiac adriamycin concentrations with a shorter tissue half-life and decreased cardiac AUC and a greater degree of hepatic metabolism to inactive 7-deoxyaglycones. The tumour peak drug level and AUC was similar irrespective of the mode of administration of adriamycin. The growth delay (i.e. the time taken for the tumour volume to double) was significantly longer for adriamycin (15 days) and niosomal adriamycin (11 days) than for control (5.8 days). It is possible that the therapeutic ratio of adriamycin could be enhanced by administration in niosomal form. (Gregoriadis, 1976; Rahman et al., 1982) are examples. There is no doubt that in most cases the pharmacokinetics of the anticancer drug are altered, sometimes favourably, with a resultant decrement in toxicity. However, a number of problems remain to be overcome to provide a clinically useful carrier system, which include questions of (a) the specificity of the carrier for tumour cells in vivo, (b) the stability of the carrier complex in vivo, (c) the release of the active agent at the target site, (d) non-specific uptake of exogenous material by the reticuloendothelial systems (Poste, 1983) and (e) adverse immunological reactions to the exogenous carrier.A number of studies have demonstrated enhanced cytotoxicity of liposome-encapsulated drugs in vitro (Kimelberg & Mayhew, 1978). It has been proposed that this effect is mediated via increased cellular drug uptake by a fusional or endocytic process. However, there is controversy over the ability of liposomes to diffuse from the vascular compartment to the tumour interstitium or whether they would be phagocytosed by cells of the reticuloendothelial system. There is in vivo evidence, however, that administration of liposomes to tumour bearing rodents decreases adriamycin associated cardiac toxicity without loss of therapeutic effect (Forssen & Tokes, 1983;Olsen et al., 1982). A preliminary report of a phase I clinical study with liposome-associated adriamycin indicated that liposome administration is feasible and has potential advantages over free adriamycin with regard to some of its immediate toxic side effects (Gabizon et al., 1986 , 1985) and these preparations are used here. In this ...
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