Propoxylation of cationic polymers provides a novel approach to controllable modulation of their cellular toxicity and interaction with nucleic acids.
An effective chemical approach to modulation of biological interactions of cationic polymers was proposed and tested using polyethyleneimine (PEI) as a drug carrier. Branched 25kDa PEI was modified in the reaction with propylene oxide (PO) to produce a series of propoxylated PEIs with NH groups grafted by single or oligomer PO units. Clear relationships between the propoxylation degree and biological effects, such as interaction with plasmid DNA, hemolytic, cytotoxic, and pro-apoptotic activities were revealed for PEIs modified upon PO/NH molar ratio of 0.5, 0.75, 1.0 and 3.0. The partial modification of available cationic centers up to 100% is predominantly accompanied by a significant gradual reduction in polycation adverse effects, while ability of complex formation with plasmid DNA is being preserved. Grafted PEI with 0.75 PO/NH ratio provides better protection from nuclease degradation and transfection activity compared with other modified PEIs. Revealed relationships contribute to the development of safe polymeric systems with controllable physicochemical properties and biological interactions.
Scientific and Educational Centre of Pharmaceutics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
Vesta D
VD
Shevchenko
Scientific and Educational Centre of Pharmaceutics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
Diana V
DV
Salakhieva
Scientific and Educational Centre of Pharmaceutics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
Abdulla A
AA
Yergeshov
Scientific and Educational Centre of Pharmaceutics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
Yuriy V
YV
Badeev
Scientific and Educational Centre of Pharmaceutics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
Yurii G
YG
Shtyrlin
Scientific and Educational Centre of Pharmaceutics, Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia. Electronic address: tabdulli@gmail.com.
Timur I
TI
Abdullin
D017209:Apoptosis / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry* / Q000633:toxicity; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D003850:Deoxyribonuclease I / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D004852:Epoxy Compounds / Q000737:chemistry; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D057809:HEK293 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry* / Q000633:toxicity; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014162:Transfection
D001672:Biocompatible Materials; D002412:Cations; D004337:Drug Carriers; D004852:Epoxy Compounds; D011094:Polyethyleneimine; D003850:Deoxyribonuclease I; C009068:propylene oxide
Biocompatibility; Cationic polymers; Cellular toxicity; Gene delivery; Polyethyleneimine; Propoxylation