The influence of the route of administration and liposome composition on the potential of liposomes to protect tissue against local toxicity of two antitumor drugs

The present paper reports on the influence of the route of administration and liposome stability on the protective effect of liposome encapsulation of two model antitumor agents, mitoxantrone and doxorubicin. The results demonstrate that liposome encapsulation can protect surrounding tissue from the cytotoxic effects of the drugs after subcutaneous (sc) and intramuscular (im) administration. The route of administration is an important factor influencing tissue damage. Liposomal mitoxantrone caused much less tissue irritation after im injection than after sc injection. Liposome stability is also an important factor. Liposomes composed of 'fluid-state' phospholipids only delayed the damaging effects of doxorubicin when injected sc. Liposomes with a more rigid nature 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 local tissue damage. The incorporation of the hydrophilic lipid derivative distearolyphosphatidylethanolamine-poly(ethyleneglycol) (PEG-PE) had no apparent effect on the protective effect of liposomes after sc administration. (C) 1998 Elsevier Science B.V.