N-(2-Hydroxypropyl)methacrylamide (HPMA) copolymers and polycations, such as poly-L-lysine, have been proposed as potential drug delivery systems. HPMA copolymers were synthesised to contain a low percentage of tyrosinamide residues facilitating their radioiodination, and in one case also containing a cationic group. The effect of the cationic residue on the association of copolymer with rat visceral yolk sacs incubated in vitro was studied. Cationic HPMA copolymer was found to associate progressively with the tissue over a five hour incubation period. Inhibitor studies (low temperature or addition of 2,4-dinitrophenol (50 μg/ml) indicated that this association was not primarily due to pinocytic capture of polymer, but due to adsorption onto the cell surface. Addition of non-radiolabelled cationic copolymer to the incubation medium did not in itself affect the rate of fluid-phase pinocytosis in yolk sac cells. Release of previously accumulated cationic copolymer from the tissue was shown to be rapid and consistent with desorption from the cell surface. Following intravenous administration to rats, the clearance of cationic copolymer from the bloodstream was rapid, the majority of radioactivity being recovered in the liver
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