Exploring Mucoadhesive and Toxicological Characteristics Following Modification of Linear Polyethylenimine with...

Area of Science:

• Polymer Chemistry
• Biomaterials Science
• Nanotechnology

Background:

• Linear polyethylenimine (L-PEI) is widely used but exhibits high toxicity and low biocompatibility due to secondary amine groups.
• Modification of L-PEI is crucial for enhancing its functionality and reducing adverse effects in applications like gene delivery and pharmaceutical formulations.

Purpose of the Study:

• To synthesize and characterize novel L-PEI derivatives using various organic anhydrides.
• To evaluate the mucoadhesive properties, aqueous behavior, and toxicity of the modified L-PEI polymers.

Main Methods:

• L-PEI was modified with methacrylic, crotonic, maleic, and succinic anhydrides.
• Structural characterization via ¹H NMR and FTIR spectroscopy.
• Aqueous solution behavior (turbidity, electrophoretic mobility), mucoadhesion (fluorescence flow through), toxicity (planaria, MTT assay), and irritancy (slug mucosa assay) were assessed.

Main Results:

• Methacrylated and crotonylated L-PEI exhibited strong mucoadhesion at pH 7.4, attributed to covalent bonding with mucin.
• Maleylated and succinylated L-PEI showed poor mucoadhesion above their isoelectric point due to electrostatic repulsion.
• Anhydride modification effectively mitigated the inherent toxicity and irritancy of L-PEI.

Conclusions:

• Organic anhydride modification is a viable strategy to reduce L-PEI toxicity and enhance mucoadhesion.
• The choice of anhydride and resulting polymer structure dictates mucoadhesive properties and pH-dependent behavior.
• Modified L-PEI derivatives show promise for advanced biomedical applications requiring improved biocompatibility and targeted delivery.