Improved stability of polycationic vector by dextran-grafted branched polyethylenimine

Area of Science:

• Biomaterials Science
• Gene Delivery
• Polymer Chemistry

Background:

• In vivo instability of polycationic vectors limits their efficacy in systemic gene delivery.
• Conjugating neutral hydrophilic polymers to polycationic vectors can improve stability by reducing interactions with blood components like serum albumin.

Purpose of the Study:

• To evaluate the effectiveness of dextran-grafting on polyethylenimine (PEI) for enhancing the stability of DNA-polymer complexes.
• To assess the impact of dextran molecular weight and grafting density on complex stability in the presence of bovine serum albumin (BSA).

Main Methods:

• Linear and branched polyethylenimines (PEI) were grafted with dextrans of 10000 (dex-10000) and 1500 (dex-1500) molecular weights.
• DNA-polymer complexes were prepared using these modified polymers at various DNA to polymer ratios.
• Complex stability was evaluated by measuring changes in size and zeta-potential, and DNA release upon exposure to BSA.

Main Results:

• Only dextran-grafted branched PEI effectively improved the stability of DNA-polymer complexes in the presence of BSA.
• Dex-10000 provided superior shielding against BSA-induced aggregation compared to dex-1500.
• The dextran-grafted branched PEI maintained complex sizes within 200 nm and zeta-potentials near neutral.

Conclusions:

• Dextran-grafted branched PEI significantly enhances the stability of DNA-polymer complexes against serum albumin.
• Higher molecular weight dextran (dex-10000) offers better protection.
• These modified polymers show potential for conjugation with ligands for targeted in vivo gene delivery.