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.

Lipid-like trifunctional block copolymers of ethylene oxide and propylene oxide: effective and cytocompatible modulators of intracellular drug delivery.

A new glycerol-based trifunctional block copolymer (TBC) of propylene oxide and ethylene oxide and its conjugate with succinic acid (TBC-SA) were studied as a drug delivery system and compared with Pluronic L61. TBCs have multiple effects on the plasma membrane of human cells, e.g. increasing its fluidity and ion permeability, inhibiting ATPase activity of efflux transporter P-glycoprotein through reversible membrane destabilization. Such membrane-modulating properties attributed to the unimer form of copolymers increase in the order Pluronic L61≪TBC