Fine Multiple Emulsions Bearing 6-Mercaptopurine: In Vitro and In Vivo Antitumor Studies

Fine multiple emulsions were prepared by a two-step emulsification using the sonication technique. 6-mercaptopurine (6-MP) was encapsulated in the internal aqueous phase. It was coated with a phospholipid derivative of polyethylene glycol (PEG-PC). The coated multiple emulsion was characterized for antitumor activity on the murine leukemia cell line L-1210 in vitro. A decreased uptake and cytotoxicity were observed for PEG-PC-coated multiple emulsion in vitro, compared with uncoated ones. The IC50 (50% inhibitory concentrated) was also decreased 1.64 times. In vivo antitumor activity was recorded as mean survival time (MST) of mice injected intravenously or intraperitoneally with tumor cells or, treated with 6-MP formulations through similar routes. MST was increased upon treatment. The normal peritoneal cells remained unchanged while blood parameters were restored with multiple emulsion treatment to tumor-bearing mice. The efficacy of the formulation was mainly due to the slow release and effective deliv...