Alginate/methacrylic acid/calcium ion-based pH-sensitive drug delivery hydrogel for the treatment of ulcerative colitis

Abstract

Oral colon-targeted drug formulations play a pivotal role in managing colon diseases, yet the effectiveness of most hydrophobic drug formulations in reaching the colon orally is hindered by challenges such as poor solubility, premature release in the stomach, and low bioavailability. In this study, we devised a pH-sensitive dual-network hydrogel utilizing sodium alginate and methacrylic acid for treating ulcerative colitis. The primary rigid network layer is activated thermally through free radicals, while the secondary flexible network layer is formed by the coordination of alginic acid and calcium ions. Sulfadiazine was loaded into the hydrogels using a solution displacement method. We conducted a comprehensive analysis of the morphology, mechanical properties, and drug release mechanisms of the hydrogels. The hydrogel demonstrated outstanding pH-responsive swelling properties. In acidic environments, protonation of carboxyl groups led to hydrogel network contraction, while in weakly alkaline environments, deprotonation induced electrostatic repulsion, facilitating swelling and controlled drug release. The alteration of pH from 1.2 to 7.4 increased the drug release rate from 33 % to 92 %, aligning with the first-order kinetic release model. The drug-loaded gel exhibited a compressive stress of 0.13 MPa at 50 % strain, and its superior mechanical properties ensured stability before drug release. Moreover, the hydrogel displayed excellent biocompatibility, hemocompatibility, and thermal stability. In summary, these findings underscore the substantial potential of drug-loaded gels in advancing controlled drug delivery systems.