PEI grafted hyperbranched polymers with polyglycerol as a core for gene delivery

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Gene Therapy Vectors

Background:

• Polyethylenimines (PEIs) are widely used in gene delivery but often exhibit toxicity.
• Developing safer and more effective non-viral gene delivery vectors is crucial for therapeutic applications.

Purpose of the Study:

• To synthesize and characterize novel hyperbranched polymers, PG6-PEI25k and PG6-PEI800, by grafting polyethylenimines (PEIs) onto a polyglycerol (PG6) core.
• To evaluate the DNA binding capability, complex formation, transfection efficiency, and cytotoxicity of these new PG6-PEI polymers.
• To compare the performance of PG6-PEI polymers against their non-grafted PEI counterparts.

Main Methods:

• Synthesis of hyperbranched polymers (PG6-PEI25k, PG6-PEI800) via grafting.
• Structural characterization using 1H NMR and FTIR spectroscopy.
• DNA binding assessed by agarose gel electrophoresis retardation assay.
• Complex characterization via Transmission Electron Microscopy (TEM) and particle size analysis.
• In vitro transfection efficiency and cytotoxicity evaluated in 293T and HeLa cell lines using reporter plasmids.

Main Results:

• Successful synthesis and structural confirmation of PG6-PEI25k and PG6-PEI800.
• Demonstrated DNA binding capability for both synthesized polymers.
• Characterization of PG6-PEI/DNA complexes showing suitable morphology and size.
• PG6-PEI25k and PG6-PEI800 exhibited enhanced transgene expression compared to PEI25k and PEI800.
• Reduced cytotoxicity was observed for PG6-PEI polymers relative to PEI controls.

Conclusions:

• PG6-PEI hyperbranched polymers represent a promising class of non-viral vectors for gene delivery.
• Grafting PEI onto a polyglycerol core significantly improves transfection efficiency and reduces cytotoxicity.
• These findings highlight the potential of PG6-PEIs as effective and safer alternatives for gene therapy applications.