Targeting drugs to hepatocytes in the liver

Details Targeting drugs to hepatocytes in the liver Targeting drugs to hepatocytes in the liver

1989-01-31

1991-06-25

Cashion, Jr., Merrell C.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

A61K 3722

Patent

active

050265580

ABSTRACT:
An improved method for selectively targeting a substance either to the parenchymal cells or the non-parenchymal cells of the liver makes use of the property that there are two pathways for uptake of liposomes by the liver: a saturable pathway involving phagocytosis and mediated by the Kupffer cells, and a non-saturable pathway involving pinocytosis and mediated by the parenchymal cells. The substance to be targeted is administered in carrier liposomes having a diameter of less than about 200 nm and a half-life in the circulation of at least about 5 hours as measured at an injection dose of about 30-50 micrograms of lipid per gram of body weight. The substance can be targeted to the parenchymal cells by administering it in carrier liposomes at a liposomal lipid dose expressed in micrograms of lipid per gram of body weight at least equal to a critical liposomal lipid dose, typically about 7 micrograms per gram of body weight to about 10 micrograms per gram of body weight. The substance can also be targeted to the parenchymal cells by selectively blocking the saturable pathway by the action of a blocking agent. The substance can be targeted to the non-parenchymal cells by administering it in carrier liposomes at a dose sufficiently lower than the critical lipid dose, typically 0.30 .mu.g of lipid per gram of body weight or less. The substance can be a polypeptide, a polynucleotide, a carbohydrate, or a drug, such as an antiviral drug.

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