The effect of liposome-entrapped specific cell growth inhibitor (chalone) on tumour cell proliferation.

The effect of specific cell growth inhibitor (chalone) on the mitotic activity of ascites ISM applied entrapped in liposomes compared to the non-entrapped 'free' form was investigated. The 'free' chalone injected intraperitoneally in BALB/c ascites ISM-bearing mice (1500 mg per kg body weight) decreased the mitotic activity of the tumour by 66 per cent 2.5 h after administration. Five hours after administration, complete restoration of the mitotic index to the control level was observed. Chalone encapsulated into Bangham liposomes (1000 mg per kg body weight) in otherwise identical conditions produced 44 per cent inhibition after 2.5 h, while at 5 h post-injection the mitotic inhibition was still present increasing up to as much as 50 per cent. No such effect was evident by chalone encapsulated in freeze-thawed liposomes (500 mg per kg body weight). The chalone under study specifically inhibits the cell division of the originating tumour cells and has no effect on its DNA synthesis or on the mitosis of the basal layer of the oesophagus and crypts of the intestinal epithelium. The results obtained provide evidence that liposome-entrapped chalone prolongs the inhibition of tumour cell mitosis in comparison to the 'free' one even in a reduced dose. Some possible applications of this approach concerning cancer research and treatment are discussed.

Brain, liver and spleen detection of liposomes after rectal administration.

Bangham-type liposomes, undergoing freeze-thawing cycles, were detected electron microscopically in the brain, liver and spleen of experimental animals 24 h after rectal administration. This novel approach has several important advantages over intravenous, intraperitoneal and other usual means of administration of liposome drug-entrapped treatment and diagnostics for human application. The location of the liposomes in the brain after rectal administration shows that the brain-blood barrier can be overcome successfully by this method. Moreover, the risk of embolism and hypersensitivity, strict control of sterility and some other undesirable effects can be avoided. The possible role of rectal administration in the development of liposome drug-entrapped treatment and diagnostics is discussed.