# Quaternized Chitosan Crosslinked Networks for pH-Responsive Macromolecule Delivery: A Review

## TL;DR

This review discusses how quaternized chitosan networks can be used for pH-responsive delivery of macromolecules in packaging and therapy.

## Contribution

The paper introduces green crosslinkers and dual pH/enzyme responsive mechanisms for intelligent chitosan-based materials.

## Key findings

- Dynamic covalent networks with quaternized chitosan improve pH responsiveness and mechanical strength.
- Schiff-base and hydrogen-bonding mechanisms enable dual (pH/enzyme) responsive release of macromolecules.
- Green crosslinkers like genipin help tailor network properties while addressing biosafety for clinical use.

## Abstract

Chitosan, a biocompatible and biodegradable polysaccharide, exhibits notable antibacterial properties. However, its practical applications are often constrained by inherent limitations such as poor solubility (restricted to acidic media) and suboptimal mechanical strength. By constructing dynamic covalent networks with QCS and green crosslinkers (e.g., genipin, dialdehyde cellulose), materials acquire excellent pH-responsive intelligence. This review elaborates on the molecular design, crosslinking strategies, and applications in intelligent packaging and targeted therapy. The synergistic Schiff-base/hydrogen-bonding mechanism enables dual (pH/enzyme) responsive release. We clarify the relationship between quaternization degree and cytotoxicity as a key challenge for clinical translation and analyze how green crosslinkers are molecular bridges to tailor network properties. The ‘perception-response’ integrated design principle of QCS demonstrates significant potential for intelligent packaging and antibacterial−anticancer synergistic therapy, while addressing key biosafety considerations.