DEVELOPMENT OF FUNCTIONAL RES-AVOIDING LIPOSOMES AND THEIR USE IN CANCER THERAPY

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Liposomes have been used as drug carriers in the field of drug delivery system (DDS).In this research, we focused on the effective targeting of liposomes and effective release of liposomal contents at the target site.At first, we developed thermosensitive liposomes which could release macromolecules encapsulated.Thermosensitive liposomes have been developed using saturated phospholipids of which phase transition temperature is slightly hygher than body temperature. We succeeded macromolecule release from these liposomes by the increase of internal osmotic pressure.Secondly, we applied RES-avoiding liposomes which had been developed by ourselves on the cancer therapy.RES-avoiding liposomes are known to be accumulated in tumor tissued by passive targeting, since they tend to reside in bloodstream and to leak out into tumor tissues through leaky endothelium.In fact, adriamycin-encapsulated RES-avoiding liposomes caused suppression of tumor volume, reduction of side effect, and prolonging of survial time in tumor-bearing mice.Multi-dose administration of the liposomes caused 40% curing of the animal.We also developed a hydrophobic anticancer prodrug, which is ready to be incorporated in liposomes, and observed the therapeutic effect of the drug.Our results progress the practical usage of functional liposomes in DDS field.