Synthesis And Characterization Of Amphiphilic Graft Copolymers As Gene/Drug Co-delivery Carries

Non-viral gene-delivery systems are safer to use and easier to produce than viral vectors, but their comparatively low transfection efficiency has limited their applications. Co-delivery of drugs and gene has been proposed to enhance gene expression or to achieve the synergistic/combined effect of drug and gene therapies. The research of co-delivery has become a hot topic. In this paper, we have successfully prepared and characterized some amphiphilic grafting copolymers, which can be used as promising co-delivery carriers for gene and drug. The major research work and conclusions are outlined as follow:1. The graft copolymer of polyethylene glycol-g-polyethyleinimine-g-chitosan (PEG-g-PEI-g-CHI) was synthesized through the coupling grafting reactions between polyethylene glycol, polyethyleinimine and O-carboxymethylated chitosan. And then the nanoparticles of the copolymer was prepared by the method of ionotropic gelation. The effects of the concentrations of the copolymer and tripolyphosphate (TPP), and the pH on the preparation of the nanoparticles were investigated. And all the synthesized compounds were characterized by nuclear magnetic resonance (1H NMR) spectroscopy and infrared spectroscopy (IR). The morphologies and size distribution of nanoparticles were quantified using images from scanning electron microscope (SEM). SEM images show that the copolymer can form good dispersion and uniform spherical particles in size of between 30 and 50 nm under the condition of the pH value of 4.0-6.0, the polymer concentration of 1-5 mg·mL-1 and TPP concentration of 0.3-1.5 mg·mL-1.2. The heterobifunctional polyethylene glycol (PEG) was prepared by anionic ring-opening polymerization of ethylene oxide using alkali metal as initiator, and the grafting copolymer (PEG-g-CHI) was prepared through the grafting reaction of the heterobifunctional PEG and chitosan (CHI). The aldehyde-functonalized PEG-g-CHI-CHO polymer was prepared through the reaction of PEG-g-CHI and p-aminobenzaldehyde. All the compounds were characterized by 1H NMR and FT-IR. The aldehyde-functonalized PEG-g-CHI-CHO polymer can further react with drug molecules possessing amino groups to generate pH-sensitive Schiff base conjugates, which may provide the possibility of controlled release of targeted drugs in vivo.3. A kind of amphiphilic block copolymer, polyethylene glycol-b-polyacrylic acid (MPEG-b-PAA) was prepared from polyethylene glycol and acrylic acid through the reversible addition fragmentation chain transfer (RAFT) polymerization using low cost and easily available 2-chloro-acetyl chloride to synthesize chain transfer agent, and then the block copolymer grafted with chitosan to get polyethylene glycol-b-polyacrylic acid-g-chitosan (MPEG-b-PAA-g-CHI) copolymer. All the compounds were characterized by 1H NMR and FT-IR.Because the these polymers mentioned above possess amino groups for binding gene and free carboxyl or aldehyde groups for binding drug, the resulted copolymers show the potential to act as co-delivery carriers for gene and drug.