Modification of vesicle surfaces with amphiphilic sterols. Effect on permeability and in vivo tissue distribution

In this paper, we describe the permeability of vesicles prepared with various synthetic cholesterol derivatives. Cholesterol derivatives with side-chains ending in hydroxyl groups reduced the permeability of unilamellar vesicles. However, addition of cholesterol derivatives with terminal amino groups makes the vesicles more permeable. Vesicles prepared with a short-chain amino-cholesterol derivative were found to be less permeable in phosphate-buffered saline, but not in bovine serum, while long-chain amino-cholesterol-containing vesicles were very permeable in both media. Studies in vivo indicate a rapid clearance rate for intravenously administered amino-cholesterol-containing vesicles with a concomitant increase in liver uptake. However, no difference was found in either the clearance or tissue distribution of control vesicles and the less permeable hydroxyl-cholesterol-containing vesicles.