DNA delivery systems based on copolymers of poly (2‐methyl‐2‐oxazoline) and polyethyleneimine: Effect of polyoxazoline moieties on the endo‐lysosomal escape. Issue 45 (22nd June 2020)

• Record Type: Journal Article
• Authors: Haladjova, Emi; Smolíček, Maroš; Ugrinova, Iva; Momekova, Denitsa; Shestakova, Pavletta; Kroneková, Zuzana; Kronek, Juraj; Rangelov, Stanislav
• Is Part Of: Journal of applied polymer science. Volume 137:Issue 45(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-06-22
• Subjects: biomedical applications -- colloids -- drug delivery systems -- nucleic acids -- polyelectrolytes; Polymers -- Periodicals; Polymerization -- Periodicals; 668.9
• DOI: 10.1002/app.49400
• Languages: English
• ISSNs: 0021-8995

Abstract

Abstract: Poly(2‐methyl‐2‐oxazoline)‐polyethylenimine (PMeOx‐co‐PEI) copolymers differing by degree of polymerization (DP = 50 and 200) and PEI content (from 37 to 99 mol%) were synthesized by living cationic ring‐opening polymerization of 2‐methyl‐2‐oxazoline, followed by partial hydrolysis. Upon mixing with DNA in a wide range of N/P ratios, they formed well‐defined polyplex particles of small size (typically below 100 nm) and narrow size distribution. The polyplexes demonstrated good colloidal stability and very low in vitro cytotoxicity. The copolymers exhibited buffering capacity of over 50% relative to that of the reference PEI implying effective endo‐lysosomal escape of the polyplexes. Increased cellular internalization of both PCR fragments and plasmid DNA, attributable to the strongly positive ζ potential and small size of the polyplexes, was observed. In spite of these favorable prerequisites, the transfection efficiency was low (below 20% relative to the control PEI) and was attributed to retarded swelling of the polyplex particles, endo‐lysosomal rupture, and DNA release. Abstract : Poly(2‐methyl‐2‐oxazoline‐co‐ethyleneimine) (PMetOx‐co‐PEI) copolymers of different composition form well‐defined, colloidally stable, biocompatible, and nontoxic polyplex particles with DNA. The systems exhibit excellent cellular uptake, however, the transfection efficiency is not satisfactory. This is attributed to the PMetOx moieties, which retard a cascade of subsequent inter‐related events in gene delivery—swelling and loosening of the polyplex particles, endo‐lysosomal escape, and release of DNA.