Synthesis of tetraarm star block copolymer based on polytetrahydrofuran and poly(2-methyl-2-oxazoline) for gene delivery applications

• Published in: European polymer journal 2017-03, Vol.88, p.689-700
• Main Authors: Rasolonjatovo, Bazoly, Pitard, Bruno, Haudebourg, Thomas, Bennevault, Véronique, Guégan, Philippe
• Format: Article
• Language: English
• Subjects: Block copolymers; Cancer; Cationic polymerization; Chains (polymeric); Chemical synthesis; Copolymers; CROP; Formulations; Gene therapy; Life Sciences; Poly(2-methyl-2-oxazoline); Polymerization; Polytetrahydrofuran; Quenching
• ISSN: 0014-3057; 1873-1945
• DOI: 10.1016/j.eurpolymj.2016.09.042

[Display omitted] •Synthesis of new tetraarm star block copolymers based on PTHF and PMeOx blocks.•The transfection efficiency of the complex DNA/star copolymers was investigated.•A transfection efficiency as high as 3% Lutrol® formulations was observed.•Low amount of star copolymer was necessary compared to 3% Lutrol® formulations. New star shaped block copolymers were synthesized according to a core first strategy, with a hydrophobic polytetrahydrofuran (PTHF) central block and a poly(2-methyl-2-oxazoline) (PMeOx) external block. First, the cationic polymerization of THF was initiated from a tetrafunctional triflate ester synthesized in situ. The chain ends were functionalized by quenching the polymerization with an excess of MeOx, that allowed for the MeOx polymerization under microwave in a subsequent step. Demonstration of the expected structures was carried out at each step of the polymerization. The controlled molar mass of the star copolymers was kept below 5000gmol−1 in order to mimick the structure of the efficient poloxamines for gene transfer applications. Formulations containing various concentrations of star block copolymers were intramuscularly injected in mice. Efficient gene transfer was measured at formulations with very low concentration of copolymer compared to reference standard containing Lutrol®.