Agent Targeting by Means of the Chemically or Physically Directed, Fusogenic Liposomes

Abstract

Based on the concept of rational membrane design it is proposed how to develop liposomes suitable for the targeting in vitro and in vivo. Such targeting can rely on the chemical or physical 'pointers'. Hyperthermia is a particularly convenient example of the latter, suggesting that thermolabile fusogenic liposomes should be devised and used for the agent delivery into cells. The resulting efficacy depends on the extent to which the phase characteristics of the fusogenic lipid membrane are made to fit the delivery-triggering signal: increasing the temperature and/or lowering the pH-value in the investigated system are most useful for this purpose, the role of membrane defects, such as may arise during the liposome manufacturing process or in the vicinity of lipid phase transitions also being of extreme importance. Thermolabile fusogenic liposomes prepared from the stoichiometric 1/2 mixture of diacylphos-?hatidylcholines with appropriate fatty acids implement these requirements. 'heir temperature dependence permitting physical targeting and their pH-dependence being suitable for the 'chemical targeting' to the acidic surrounding. Dipalmitoylphosphatidylcholine/elaidic acid mixture is, perhaps, the best such combination for the use in vivo. The efficacy of fusion between the corresponding lipid vesicles and cells in vitro as well as the delivery of radioactive labels into the heated tumours (but not in the normal muscle tissue with the inpenetrable micro-vasculature) provide compelling evidence for this.