EVALUATION OF BLOOD CLEARANCE RATES AND BIODISTRIBUTION OF POLY(2-OXAZOLINE)-GRAFTED LIPOSOMES

Two amphipatic polymers of the poly(2-oxazoline) family, poly(2-methyl -2-oxazoline) (PMOZ) and poly(2-ethyl-2-oxazoline) (PEOZ), were synthe sized with the carboxylic group positioned at either the initiation or termination ends of the polymer chains. Distearoylphosphatidylethanol amine was covalently linked to the carboxyl groups of the polymers, re sulting in conjugates which incorporate readily into liposomes. System atic evaluation of plasma clearance kinetics and biodistribution of li posomes containing hydrogenated soy phosphatidylcholine, cholesterol, and 5 mol % the polymer-lipid conjugates in mice revealed the followin g. Both polymers, PMOZ and PEOZ, exhibited long plasma lifetimes and l ow hepatosplenic uptake. PMOZ was more effective at decreasing blood c learance rates than PEOZ. The best results, which were quantitatively comparable to the results obtained with the optimized preparations of methoxypolyethylene glycol(PEG)-2000-grafted liposomes, were obtained with formulations containing PMOZ of molecular weight 3260.