Synthesis of Double Hydrophilic Block Copolymers Poly(2‐isopropyl‐2‐oxazoline‐b‐ethylenimine) and their DNA Transfection Efficiency

• Published in: Macromolecular bioscience 2023-01, Vol.23 (1), p.e2200296-n/a
• Main Authors: Delecourt, Gwendoline, Plet, Laetitia, Guen, Yann Le, Tezgel, Ozgul, Tresset, Guillaume, Midoux, Patrick, Montier, Tristan, Bennevault, Véronique, Guégan, Philippe
• Format: Article
• Language: English
• Subjects: Aziridines; Block copolymers; Chemical Sciences; Chemical synthesis; Copolymers; Cytotoxicity; Deoxyribonucleic acid; DNA; Drug delivery; Drug delivery systems; Efficiency; Expression vectors; Galenic pharmacology; gene therapy; Gene transfer; Gene Transfer Techniques; Histidine; Life Sciences; oxazoline; PEGylation alternative; PEI; Pharmaceutical sciences; Plasmids; Polyethyleneimine; Polyethyleneimine - pharmacology; Polymers; Steric hindrance; Toxicity; Transfection; Vaccination
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.202200296

Gene delivery is now a part of the therapeutic arsenal for vaccination and treatments of inherited or acquired diseases. Polymers represent an opportunity to develop new synthetic vectors for gene transfer, with a prerequisite of improved delivery and reduced toxicity compared to existing polymers. Here, the synthesis in a two‐step's procedure of linear poly(ethylenimine‐b‐2‐isopropyl‐2‐oxazoline) block copolymers with the linear polyethylenimine (lPEI) block of various molar masses is reported; the molar mass of the poly(2‐isopropyl‐2‐oxazoline) (PiPrOx) block has been set to 7 kg mol−1. Plasmid DNA condensation is successfully achieved, and in vitro transfection efficiency of the copolymers is at least comparable to that obtained with the lPEI of same molar mass. lPEI‐b‐PiPrOx block copolymers are however less cytotoxic than their linear counterparts. PiPrOx can be a good alternative to PEG which is often used in drug delivery systems. The grafting of histidine moieties on the lPEI block of lPEI‐b‐PiPrOx does not provide any real improvement of the transfection efficiency. A weak DNA condensation is observed, due to increased steric hindrance along the lPEI backbone. The low cytotoxicity of lPEI‐b‐PiPrOx makes this family a good candidate for future gene delivery developments. The synthesis of linear lPEI‐b‐PiPrOx block copolymers with various molar masses PEI block is reported. Plasmid DNA condensation is successfully achieved, and in vitro transfection efficiency of the copolymers is at least comparable to that obtained with the lPEI of same molar mass. The low cytotoxicity of lPEI‐b‐PiPrOx makes this family a good candidate for future gene delivery developments.