Development and Optimization of Stimuli-Responsive Fenugreek/Carrageenan-Co-poly (Methacrylate) Hydrogel Matrices for Controlled Delivery of 5-Fluorouracil

Abstract

This study developed novel, stimuli-responsive, biocompatible fenugreek/carrageenanco-poly(methacrylate) hydrogels via free radical polymerization for pH-regulated 5-FU delivery. The hydrogels were evaluated for drug loading (75.2–96.39%), swelling kinetics, sol–gel fraction, electrolyte responsiveness, porosity, and in vitro drug release. Analytical techniques (FTIR, SEM, PXRD, DSC/TGA) confirmed hydrogel formation, drug-excipient compatibility, and thermal stability. FTIR verified cross-linking and 5-FU incorporation, while DSC/TGA and PXRD indicated reduced drug crystallinity and transition to an amorphous form. SEM revealed rough surfaces with porous networks, supporting high drug loading. The hydrogels exhibited pH-responsive swelling, with higher swelling at pH 7.4 (following second-order kinetics) and minimal swelling at pH 1.2. They also responded to monovalent and divalent cations. In vitro release at pH 7.4 showed controlled 5-FU delivery (68.40–96.81%) over 36 h, following non-Fickian diffusion and Higuchi kinetics. Acute oral toxicity studies confirmed biocompatibility and safety. These findings demonstrate that fenugreek/carrageenan-co-poly(methacrylate) hydrogels are promising biocompatible carriers for targeted, controlled 5-FU delivery, offering a safer option for colorectal cancer treatment and other chemotherapy regimens.

Graphical Abstract