Biodegradable branched poly(ethylenimine sulfide) for gene delivery

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Gene Delivery

Background:

• Linear poly(ethylenimine sulfide) (PEIS) is a polymer with potential applications in gene delivery.
• Developing biodegradable versions of PEIS is crucial for reducing potential cellular accumulation and toxicity.
• Controlling the degradation and properties of PEIS is essential for optimizing its use.

Purpose of the Study:

• To synthesize and characterize biodegradable branched poly(ethylenimine sulfide) (b-PEIS).
• To investigate the relationship between crosslinking degree, molecular weight, and degradation properties of b-PEIS.
• To evaluate the transfection efficiency and cytotoxicity of the synthesized b-PEIS.

Main Methods:

• Synthesis of b-PEIS via crosslinking linear PEIS using bisepoxide.
• Control of molecular weight and crosslinking degree by adjusting bisepoxide concentration.
• Degradation studies under reductive conditions (glutathione solution).
• Characterization using MALLS and gel electrophoresis.
• In vitro transfection efficiency and cytotoxicity assays.
• Intracellular trafficking studies using image restoration microscopy.

Main Results:

• Successfully synthesized biodegradable b-PEIS with tunable molecular weights and crosslinking degrees.
• Demonstrated facile degradation of b-PEIS under reductive conditions, with degradation rate dependent on crosslinking.
• Confirmed minimal loss of buffering capacity post-crosslinking.
• Achieved high gene transfection efficiency and low cytotoxicity in cellular assays.
• Observed no intracellular accumulation of b-PEIS via microscopy.

Conclusions:

• Biodegradable b-PEIS can be synthesized with controlled properties and efficient degradation.
• The developed b-PEIS exhibits promising characteristics for safe and effective gene delivery applications.
• Further research into b-PEIS could lead to advanced biomaterials for therapeutic purposes.