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Abstract
The aim of the present study was to synthesize and characterize a stabilized polymeric gene delivery carrier, a poly(ethylene glycol)-co-poly(ethylenimine) (PEG-PEI) co-polymer, using isophorone diisocyanate (IPDI) as the coupling reagent. IPDI containing two different active isocyanate functional groups could satisfy the need for a selective conjugation in the two-step coupling reaction procedure. In the first step, methoxy-poly(ethylene glycol) (mPEG) (5 kDa) was combined with one isocyanate group of IPDI to form reactivated pre-polymers, NCO-terminated mPEGs. Then branched polyethylenimine (b-PEI) (25 kDa) reacted with the isocyanate group of a varying number of NCO-terminated mPEGs, leading to PEG-PEI co-polymers with urea bonds. PEG segments in the co-polymer were designed as the stabilizers for steric stabilization of polyplexes. PEG-PEI co-polymers were identified by Fourier transform infrared spectroscopy, nuclear magnetic resonance spectroscopy and gel-permeation chromatography. The thermal properties of PEG-PEI co-polymers were characterized by differential scanning calorimetry and thermogravimetric analysis. The results indicated the existence of hydrogen bonding interaction and partial compatibility between the two phases in the PEG-PEI co-polymers. Finally, this synthetic method allowed us to prepare PEG-PEI co-polymers with the modification degree of PEG varying between 17.8% and 82.6 wt%. This new process was easy to optimize and PEG-PEI co-polymers with high yield could be obtained.
