Engineered Cyclodextrin-Starch Hydrogels for pH-Triggered Drug Release

Oral drug delivery systems must ensure that therapeutic agents reach the target site, minimizing premature release in the gastric environment. In this context, hydrogels have emerged as promising biomaterials due to their ability to swell, retain, and release drugs in response to environmental stimuli. However, optimizing hydrogel formulations, considering both the properties and the polymer-drug interactions, is challenging. Herein, starch and β-cyclodextrin (βCD) were modified with GMA to introduce polymerizable vinyl groups. The βCD was modified by transesterification, while the starch produced three distinct isomers due to additional epoxide ring-opening reactions. The modified molecules were cross-linked via free radical polymerization. A simplex-centroid design optimized the hydrogel formulations. The mathematical model could predict the composition that maximizes the difference between the swelling at pH 1.2 and 6.8. Scanning electron microscopy revealed that the porous size was dependent on the pH. The release studies of hydrocortisone indicated that only sample HG14 exhibited effective pH-responsive release, making it a promising candidate for intestinal drug delivery. Moreover, the release mechanism followed Fickian diffusion, ensuring controlled drug transport without burst release. These findings highlight the importance of optimizing the hydrogel formulation for achieving pH-responsive drug delivery and obtaining an advanced material for oral pharmaceutical applications.