Cationic lipospheres as delivery systems for nucleic acid molecules

The development of protocols aimed to obtain optimal and efficient genetic transfer have been studied and led to the production of many delivery vehicles able to bind DNA. The optimal carrier, has to accumulate at sites of diseases such as infections, inflammations and tumours, has to be a small, neutral and highly serum-stable particle. Moreover, it has to be not readily recognized by the fixed and free macrophages of the reticuloendothelial system (RES). Among non-viral systems, particulate carriers (e.g. polymeric nano- and micro-particles, fat emulsion, liposomes) possess specific advantages and disavantages. With respect to other delivery systems, microparticles (a) could maintain unaltered their physico-chemical characteristics for long periods allowing long term storage (b) can be administered through different ways (oral, intramuscular or subcutaneous) depending on their composition and (c) are suitable for an industrial production. These findings have encouraged the development of neutral and cationic lipospheres (CLS) as nonviral DNA-mediated gene transfer techniques since CLS enable the extemporaneous production of pharmaceutical formulations. This chapter discuss (a) the production and characterization of CLS obtained by different techniques, (b) the formation of the complex between CLS and DNA and finally (c) the in vitro cytotoxicity on different cell lines and the transfection efficiency of CLS. From the analysis of the results reported in the present chapter it emerges that CLS may provide a new, efficient means for the immediate intracellular delivery of therapeutic macromolecules. Nevertheless, caution is warranted for cationic carriers, which may accentuate cytotoxic effects in the phagocytic cells.