Evaluation of Blood Clearance Rates and Biodistribution of Poly(2-oxazoline)-Grafted Liposomes

• Published in: Journal of pharmaceutical sciences Vol. 85; no. 2; pp. 133 - 137
• Main Authors: Zalipsky, Samuel, Hansen, Christian B., Oaks, Jan M., Allen, Theresa M.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.02.1996; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: Animals; Biological and medical sciences; Female; General pharmacology; Kinetics; Liposomes - chemistry; Liposomes - metabolism; Medical sciences; Mice; Mice, Inbred Strains; Molecular Weight; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Polymers - chemistry; Polymers - metabolism; Tissue Distribution; Pharmaceutical technology; Rodentia; Elimination; Liposome; Drug carrier; Blood; Vertebrata; Mammalia; Mouse; Animal; Formulation; Distribution; Half life
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js9504043

Two amphipatic polymers of the poly(2-oxazoline) family, poly(2-methyl-2-oxazoline) (PMOZ) and poly(2-ethyl-2-oxazoline) (PEOZ), were synthesized with the carboxylic group positioned at either the initiation or termination ends of the polymer chains. Distearoylphosphatidyletha-nolamine was covalently linked to the carboxyl groups of the polymers, resulting in conjugates which incorporate readily into liposomes. Systematic evaluation of plasma clearance kinetics and biodistribution of liposomes containing hydrogenated soy phosphatidylcholine, cholesterol, and 5 mol % the polymer-lipid conjugates in mice revealed the following. Both polymers, PMOZ and PEOZ, exhibited long plasma lifetimes and low hepatosplenic uptake. PMOZ was more effective at decreasing blood clearance 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.