Neutral Block Copolymer Assisted Gene delivery using Hydrodynamic Limb Vein Injection.
Yann Le GuenGwendoline DelecourtTony Le GallHaiqin DuNicolas IllyCécile HuinVéronique BennevaultPatrick MidouxTristan MontierPhilippe GuéganPublished in: Macromolecular bioscience (2024)
Three different amphiphilic block copolymer families were synthesized to investigate new opportunities to enhance gene delivery via Hydrodynamic Limb Vein (HLV) injections. First a polyoxazoline-based family containing mostly one poly(2-methyl-2-oxazoline) (PMeOx) block and a second block POx with an ethyl (EtOx), isopropyl (iPrOx) or phenyl substituent (PhOx) has been synthesized. Then an ABC poly(2-ethyl-2-oxazoline)-b-poly(2-n-propyl-2-oxazoline)-b-poly(2-methyl-2-oxazoline) triblock copolymer was synthesized, with a thermosensitive middle block. Finally, polyglycidol-b-polybutylenoxide-b-polyglycidol copolymers with various molar masses and amphiphilic balance were produced. The simple architecture of neutral amphiphilic triblock copolymer is not sufficient to obtain enhanced in vivo gene transfection. Double or triple amphiphilic neutral block copolymers are improving the in vivo transfection performances through HLV administration as far as a block having an LCST is incorporated in the vector. The molar mass of the copolymer does not seem to affect the vector performances in a significant manner. This article is protected by copyright. All rights reserved.