Enhancement of Anti-metastatic Activity of Pentoxifylline by Encapsulation in Conventional Liposomes and Sterically Stabilized Liposomes in Murine Experimental B16F10 Melanoma Model

• Published in: Journal of pharmacy and pharmacology 2000-12, Vol.52 (12), p.1461-1466
• Main Authors: SANT, V. P., NAGARSENKER, M. S., RAO, S. G. A., GUDE, R. P.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Compounding; Female; General aspects; General pharmacology; Liposomes - chemistry; Lung Neoplasms - prevention & control; Lung Neoplasms - secondary; Male; Medical sciences; Melanoma, Experimental - drug therapy; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Neoplasm Metastasis - prevention & control; Pentoxifylline - chemistry; Pentoxifylline - pharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Solutions; Specific Pathogen-Free Organisms; Tumor Cells, Cultured
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/0022357001777667

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 20 mg 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.