# Thermo- and pH-Responsive Antimicrobial Hydrogels from Poly(2-(dimethylamino)ethyl methacrylate) and Cationic-Modified Chitosan for Sustained Papain Release

**Authors:** Carolina Cruz Ferreira, Guilherme Frey Schutz, Iago Aguiar Dias Carmo, Lucas Novaes Teixeira, Elizabeth Ferreira Martinez, Lúcia Helena Innocentini Mei, Roniérik Pioli Vieira

PMC · DOI: 10.1021/acspolymersau.5c00148 · 2025-12-10

## TL;DR

Researchers created a hydrogel that can release papain over time and has antimicrobial properties, which could be useful for wound dressings.

## Contribution

A novel semi-IPN hydrogel combining PDMAEMA and HTCC for sustained papain release and antimicrobial activity is developed.

## Key findings

- The 25% HTCC formulation showed nearly complete inhibition of Staphylococcus aureus.
- Papain release was diffusion-controlled, with slower release in denser networks.
- The hydrogel maintained fibroblast viability above 70%, indicating biocompatibility.

## Abstract

Semi-interpenetrating polymer networks (semi-IPNs) composed
of
poly­(2-(dimethylamino)­ethyl methacrylate) (PDMAEMA) and various concentrations
of N-(2-hydroxypropyl)-3-trimethylammonium chitosan
chloride (HTCC) (5, 10, and 25% w/w) were synthesized and evaluated
as matrices for papain loading and sustained delivery. The incorporation
of HTCC significantly influenced the structural, swelling, and release
properties of the networks. Monomer conversion and gel fraction decreased
with increasing HTCC content, reaching 91.26 and 81.36%, respectively,
at 25% HTCC. Swelling studies revealed a nonlinear behavior, with
the 5% HTCC sample exhibiting the highest swelling degree (458.33%),
while pure PDMAEMA and the 25% HTCC formulation reached 219.78 and
168.23%, respectively. Papain release profiles, fitted to the Peppas–Sahlin
model, showed diffusion-controlled kinetics, with k
1 values decreasing from 31.89 h–m
 (PDMAEMA) to 6.14 h–m
 (PDMAEMA/HTCC25%),
indicating hindered diffusion in denser networks, which may be beneficial
for a more sustained therapeutic release. Antibacterial assays confirmed
the potent activity of HTCC-containing formulations against Staphylococcus aureus, with 25% HTCC demonstrating
nearly complete inhibition (∼95%), while no significant inhibition
was observed against Escherichia coli, indicating Gram-specific selectivity. Moreover, the 25% HTCC formulation
maintained fibroblast viability above 70%, further supporting these
hydrogels as bioactive wound dressings combining controlled delivery
with antimicrobial activity.

## Linked entities

- **Proteins:** LOC110813108 (papain-like)

## Full-text entities

- **Diseases:** Swelling (MESH:D004487)
- **Chemicals:** HTCC (MESH:C550160), Cationic-Modified Chitosan (-), PDMAEMA (MESH:C407037), polymer (MESH:D011108)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Escherichia coli (E. coli, species) [taxon 562]

## Figures

20 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12903428/full.md

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Source: https://tomesphere.com/paper/PMC12903428