The Process of Milk Coagulation by Rennet

ADJ/PC6A tumour was passaged aseptically by trocar implant of 1 mm3 fragments in approx. 8-week-old female Balb 'C' mice. Then 26 days later the tumour-bearing mice were injected in the tail vein with the free or liposome-associated drug. Animals were killed 1 and 3 h after injection, and cis-dichlorobiscyclopentylamineplatinum(lI) was determined by measuring platinum in 10-5Opl samples of blood plasma and of tissues after homogenization for45 s in water (1 : 5 , w/w) in an Ultra-Turrax homogenizer. At 1 h after the administration of free cis-dichlorobiscyclopentylamineplatinum(I1) into tumour-bearing mice, tumour tissue retained only about 0.15 % of the dose/g, and there was no change 3h later (Fig. 1). It appeared that much of the drug was rapidly removed from the circulation (0.74% of the dose/ml of plasma 1 h after treatment; Fig. l), possibly as a result of the rapid clearance of the drug by the spleen (Speer et al., 1975). Clearance of the entrapped drug, however, was less rapid (Fig. 1). Indeed, participation of the tumour in cis-dichlorobiscyclopentylamineplatinum(l1) uptake was greatly improved when the drug was injected in its liposomal form. Egg phosphatidylcholine liposomes were particularly effective, as the concentration of cis-dichlorobiscyclopentylamineplatinum(I1) in the tumour increased 15-fold over the value observed for the free drug (Fig. 1). The advantage of using this preparation vis-a-vis dipalmitoyl phosphatidylcholine liposomes (Fig. 1) was also apparent when hepatic concentrations of the drug (1 and 3 h) were compared: much less cis-dichlorobiscyclopentylamineplatinum(I1) was taken by the liver when egg phosphatidylcholine liposomes were used (Fig. 1). Although this method of presentation of cis-dichlorobiscyclopentylamineplatinum(I1) has now facilitated the administration of the drug, it remains to be seen whether its tumour cytotoxicity will be proportional to its concentration in malignant tissues.