Synthesis and characterization of a sterically stabilized polyelectrolyte using isophorone diisocyanate as the coupling reagent.
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.
Shen
Yuan
Y
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, PR China.
Deng
Jingjing
J
Luo
Xin
X
Zhang
Xuan
X
Zeng
Xin
X
Feng
Min
M
Pan
Shirong
S
D002152:Calorimetry, Differential Scanning; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006860:Hydrogen Bonding; D017953:Isocyanates / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry
D004337:Drug Carriers; D017953:Isocyanates; C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; C015301:isophorone diisocyanate; D011094:Polyethyleneimine