| Abstract [eng] |
Gene therapy, as a potential method in medical diagnostics and treatment of genetic disorders such as immunodeficiency, cystic fibrosis, neurodegenerating diseases or cancer, has gained essential attention over the past decade. For gene therapy (genetic engineering) DNA or siRNA are generally inserted into cells using variety of methods and carriers. Among them, polymeric vectors were considered as the most suitable and promising due to their low immunogenicity and toxicity, possibility of repeat administration, and low production cost. Consequently, polymeric vectors for transfection of DNA and/or siRNA to cells belong to hot topics in polymer science. The ideal polymeric vector must have proper molecular weight, structure and chemical composition for achieving long circulation time, low immunogenicity, good biocompatibility, selective targeting and efficient penetration of physiological barriers. High molecular weight polyalkyleneimines were synthesized for the first time by polycondensation of aliphatic diamines and dibromides at appropriate reaction conditions. Isothermal reaction calorimetry was used to study kinetics of the polycondensation reaction. Poly(2-hydroxypropyleneimine) derivatives containing disulfide linkages in the main chain or attached MPEG chains and polyamidoamines containing hydroxyl and ethereal groups in the main chain were prepared for the first time. Newly synthesized polymers were tested as DNA or siRNA delivery agents. Transfection results showed that PHPI derivatives containing disulfide linkages in the main chain or MPEG segments could be great candidates for in vitro and in vivo transfection. |
