EFFECTS OF INTRAPERITONEAL ADMINISTRATION OF FREE AND LIPOSOME-ENTRAPPED DOXORUBICIN ON RAT PERITONEAL-EXUDATE CELL-POPULATIONS

In the present paper effects of i.p. treatment with free or liposome-e ntrapped doxorubicin (DXR) on rat peritoneal exudate cell (PEG) popula tions were examined. Two types of DXR-liposomes were used: one type co nsisting of phosphatidyicholine/phosphatidylserine/cholesterol (molar ratio 10/1/4, mean size approx. 0.3 mu m) and the other type of hospha tidylcholine/dipalmitoylglycerol/cholesterol (molar ratio 10/1/10, mea n size approx. 0.8 mu m) Dramatically fewer PEC could be recovered fro m rats given free DXR or DXR-liposomes i.p. (10 mg DXR/kg body weight) 24 h before sacrifice than from control rats. Also the ratio of leuko cyte species was modified by treatment with DXR, in free or liposomal form; in both cases the relative number of macrophages tended to incre ase. HPLC determination of the amount of DXR associated with monolayer s obtained by seeding PEC harvested after a single i.p. dose of free D XR or liposomal DXR suggests that peritoneal macrophages are not parti cularly active in endocytosing DXR-liposomes. It was observed that the peritoneal macrophages phagocytosed DXR-containing granules from degr anulating mast cells after both i.p. treatment with free DXR and DXR-l iposomes, Decreased yields of PEC following i.p. treatment with free o r liposomal DXR as well as an involvement of mast cells in the process ing of both free DXR and liposome-encapsulated DXR in the peritoneal c avity may have important consequences for approaches to i.p. chemother apy.