# Protein-Modulated Stimuli-Responsive Hydrogels Based on Methacrylated Bovine Serum Albumin and pNIPAm: pH- and Temperature-Dependent Drug Release Behavior

## TL;DR

This paper introduces a new type of hydrogel that can release drugs in response to changes in pH and temperature, making it suitable for targeted gastrointestinal drug delivery.

## Contribution

The novel contribution is the development of a dual pH- and temperature-responsive hydrogel system using methacrylated bovine serum albumin and pNIPAm for controlled drug release.

## Key findings

- Hydrogels showed dual responsiveness to pH and temperature, with drug release profiles tunable by composition.
- GEL 4 achieved the highest cumulative drug release (91%) under pH 7.4 conditions.
- Cytocompatibility tests showed improved fibroblast viability with higher MeBSA content.

## Abstract

Hydrogels are widely investigated as drug carriers for cancer therapy due to their ability to provide sustained release and reduce systemic side effects. In this study, MeBSA–PNIPAm hydrogels were developed as dual-temperature and pH-responsive systems for gastrointestinal delivery of 5-FU. MeBSA was successfully synthesized using glycidyl methacrylate and confirmed by FTIR and 1H-NMR analyses. Hydrogels with varying MeBSA/NIPA ratios were prepared via redox polymerization. DSC results showed that increasing MeBSA content shifted the phase transition temperature of hydrogels, while TGA analysis revealed enhanced thermal stability with higher MeBSA incorporation. Temperature-dependent swelling experiments further demonstrated that the VPTT slightly shifted depending on the surrounding pH, indicating that the thermoresponsive behavior of the hybrid network is influenced by the pH-dependent charge state of the protein component. Swelling studies performed at 30, 37, and 40 °C and at pH 1.2 and 7.4 confirmed dual-responsive behavior. Drug loading efficiencies above 70% were achieved for all formulations. In vitro release studies at 37 °C demonstrated distinct composition-dependent release profiles. During the first 2 h, all hydrogels exhibited controlled and limited release without burst behavior under acidic conditions. Following the transition to pH 7.4, a composition-dependent increase in drug release was observed. GEL 4 achieved the fastest and highest cumulative release (91%), whereas GEL 1 provided the most sustained release over 72 h (32%). Kinetic analysis indicated diffusion-controlled release, best described by the Weibull and Korsmeyer–Peppas models. Cytocompatibility tests showed that fibroblast viability improved with increasing MeBSA content. Overall, protein-modulated dual-responsive hydrogels offer tunable and biocompatible platforms for stimuli-responsive gastrointestinal drug delivery applications.