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

Abstract

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. Distearoylphosphatidylethanolamine 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.

Thermal Properties of Methyl Ester-Containing Poly(2-oxazoline)s

“…Poly(2-methyl-2-oxazoline) (PMeOx) and poly(2-ethyl-2-oxazoline) (PEtOx) are interesting for biomedical applications because they show stealth behaviour similar to poly(ethylene glycol) (PEG) [15,[21][22][23][24][25].…”

A Systematic Study on the Self-Assembly Behaviour of Multi Component Fmoc-Amino Acid-Poly(oxazoline) Systems

“…Fmoc has been used for its self-assembly and fluorescence properties but we envisage that it could be replace by a more biocompatible aromatic functionality still able to develop interesting self-assembly interactions through π-π stacking, e.g., fully peptidic self-assembly moieties [27]. The development of such a system could lead to application in the drug delivery field due to the low cytotoxicity profiles showed by POx family [28][29][30] and the "switchability" introduced by enzyme catalysis.…”

Polymers for Protein Conjugation

“…Poly(2-ethyl 2-oxazoline) (PEOZ) (Figure 6) is a linear synthetic polymer that is considered to be a promising substitute for PEG in view of its stealth properties [89][90][91]. PEOZ is soluble in water and in many organic solvents [92].…”