THE INFLUENCE OF THE ROUTE OF ADMINISTRATION AND LIPOSOME COMPOSITIONON THE POTENTIAL OF LIPOSOMES TO PROTECT TISSUE AGAINST LOCAL TOXICITY OF 2 ANTITUMOR DRUGS

The present paper reports on the influence of the route of administrat ion and liposome stability on the protective effect of liposome encaps ulation of two model antitumor agents, mitoxantrone and doxorubicin. T he results demonstrate that liposome encapsulation can protect surroun ding tissue from the cytotoxic effects of the drugs after subcutaneous (sc) and intramuscular (im) administration. The route of administrati on is an important factor influencing tissue damage. Liposomal mitoxan trone caused much less tissue irritation after im injection than after sc injection. Liposome stability is also an important factor. Liposom es composed of 'fluid-state' phospholipids only delayed the damaging e ffects of doxorubicin when injected sc. Liposomes with a more rigid na ture were much more effective in preventing local tissue damage over a longer period of time when administered sc. Results suggest that slow release of liposome-associated drugs may eventually cause severe loca l tissue damage. The incorporation of the hydrophilic lipid derivative arolyphosphatidylethanolamine-poly(ethyleneglycol) (PEG-PE) had no ap parent effect on the protective effect of liposomes after sc administr ation. (C) 1998 Elsevier Science B.V.