Effects of niosomal cisplatin and combination of the same with theophylline and with activated macrophages in murine B16F10 melanoma model.

The use of cisplatin is limited due to its certain toxic effects. In the present study niosomes of cisplatin by using span 60 and cholesterol were prepared and investigated for antimetastatic activity in experimental metastatic model of B16F10 melanoma. Theophylline and its combination effect with free cisplatin and niosomal cisplatin were also carried out in the same model. The effect of treatment with activated macrophages alone and in combination with cisplatin, theophylline and niosomal cisplatin was also observed. Treatment with niosomal cisplatin (1 mg/kg) and combination of the same with theophylline (15 mg/kg) showed significant reduction in the number of lung nodules as compared to untreated control as well as with free cisplatin (1 mg/kg). The treatment with activated macrophages (activated by using Muramyl dipeptide) significantly reduced the secondary growth of tumor in lung. Niosomal cisplatin showed a significant protection against weight loss and bone marrow toxicity as compared to free cisplatin. These results suggest that cisplatin encapsulated in niosomes has significant antimetastatic activity and reduced toxicities than that of free cisplatin. However theophylline failed to show antimetastatic effect alone or in combination with cisplatin or with activated macrophages.