In vivo life span of resealed rabbit erythrocyte ‘ghosts’

Abstract

Resealed erythrocyte ‘ghosts’ have been proposed as biodegradable in vivo carriers for exogenous enzymes in the therapy of inherited metabolic diseases. Extended animal studies are essential prior to clinical application. The survival of rabbit erythrocyte ‘ghosts’ has been studied to find a suitable animal model. In vitro experiments have shown that incorporation of macromolecules into rabbit erythrocyte ‘ghosts’ is much lower than into human erythrocyte ‘ghosts’. This could be related to the continous cell destruction during ‘ghost’ preparation procedures. Rapid destruction of ‘ghosts’ in the circulation was obtained in all experiments particularly in the first minutes and hours. Cells surviving this initial period showed a longer life span and kinetics of further cell destruction followed a logarithmic function similar to that of normal erythrocytes. The experimental use of rabbits appears limited to studies where rapid uptake of the enzyme is required and other animal models must be studied when prolonged survival of the erythrocyte ‘ghosts’ is required, e.g., as the site of substrate degradation in the circulation.