Partially Hydrolyzed Poly(n-propyl-2-oxazoline ... - ACS Publications

Oct 10, 2016 - NMR Centre, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academia of. Science, 1113 Sofia, Bulgaria. ⊥. Fa...
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Partially hydrolyzed poly(n-propyl-2-oxazoline): synthesis, aqueous solution properties and preparation of gene delivery systems Maarten A. Mees, Emi Radoslavova Haladjova, Denitsa Momekova, Georgi Momekov, Pavletta S. Shestakova, Christo Borissov Tsvetanov, Richard Hoogenboom, and Stanislav Miletiev Rangelov Biomacromolecules, Just Accepted Manuscript • DOI: 10.1021/acs.biomac.6b01088 • Publication Date (Web): 10 Oct 2016 Downloaded from http://pubs.acs.org on October 12, 2016

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Biomacromolecules

Partially hydrolyzed poly(n-propyl-2-oxazoline): synthesis, aqueous solution properties and preparation of gene delivery systems Maarten Meesǂ, Emi Haladjova§, Denitsa Momekova‡, Georgi Momekov‡, Pavletta S. Shestakova#, Christo B. Tsvetanov§, Richard Hoogenboomǂ* Stanislav Rangelov§* ǂSupramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry Ghent University, Krijgslaan 281 S4, B-9000 Ghent, Belgium §Institute of Polymers, Bulgarian Academia of Science, Acad. G. Bonchev St., bl. 103-A, 1113 Sofia, Bulgaria ‡Faculty of Pharmacy, Medical University of Sofia, 2 Dunav str., Sofia 1000, Bulgaria #NMR Centre, Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev St., bl. 9, 1113 Sofia, Bulgaria

KEYWORDS Poly(2-oxazoline), Polyethylenimine, Acidic hydrolysis, Polyplexes, Capsules, DNA delivery

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ABSTRACT Random copolymers of n-propyl-2-oxazoline and ethylenimine (PPrOx-PEI) were prepared by partial acidic hydrolysis of poly(n-propyl-2-oxazoline) (PPrOx). Dynamic and electrophoretic light scattering and diffusion-ordered NMR spectroscopy were utilized to investigate aqueous solution properties of the copolymers. Above a specific cloud point temperature, well-defined nanoparticles were formed. The latter consisted of a core composed predominantly of PPrOx and a thin positively charged shell from PEI moieties which mediated formation of polyplexes with DNA. The polyplexes were prepared at 65°C at varying N/P (amine-to-phosphate groups) ratios. They underwent structural changes upon temperature variations 65 – 25 – 37°C depending on N/P. At N/P