Enhancement of anti-metastatic activity of pentoxifylline by encapsulation in conventional liposomes and sterically stabilized liposomes in murine experimental B16F10 melanoma model.

Abstract

Pentoxifylline has been shown to exhibit anti-metastatic activity by inhibiting homing of B16F10 melanoma cells in the murine experimental metastasis model. In this study, the effect of encapsulation of pentoxifylline in conventional and sterically stabilized liposomes on its anti-metastatic activity in the murine experimental metastasis model was investigated. After a single intravenous dose (10, 20 or 40 mg kg(-1)), pentoxifylline solution, as well as conventional pentoxifylline liposomes, significantly reduced the number of pulmonary nodules compared with the untreated control group. Conventional pentoxifylline liposomes showed significantly higher inhibition (69%) of pulmonary tumour nodule formation at a dose of 20mg kg(-1) as compared with pentoxifylline solution (49%) at the same dose. Encapsulation of pentoxifylline in sterically stabilized liposomes prepared by incorporation of monomethoxypolyethyleneglycol (5000)-cholesteryl ester further enhanced the inhibition of pulmonary nodule formation (77%) at a dose of 20 mg kg(-1) as compared with conventional pentoxifylline liposomes. Overall, the results suggest that encapsulation of pentoxifylline in conventional liposomes enhanced its anti-metastatic activity. Steric stabilization of pentoxifylline liposomes also resulted in a two-fold increase in anti-metastatic activity (at dose of 10 mg kg(-1)) as compared with conventional liposomes.