Ellagic Acid Inclusion Complex-Loaded Hydrogels as an Efficient Controlled Release System: Design, Fabrication and In Vitro Evaluation

Abstract

Oxidants play a crucial role in the development of oxidative stress, which is linked to disease progression. Ellagic acid is an effective antioxidant with applications in the treatment and prevention of several diseases, since it neutralizes free radicals and reduces oxidative stress. However, it has limited application due to its poor solubility and oral bioavailability. Since ellagic acid is hydrophobic, it is difficult to load it directly into hydrogels for controlled release applications. Therefore, the purpose of this study was to first prepare inclusion complexes of ellagic acid (EA) with hydroxypropyl-β-cyclodextrin and then load them into carbopol-934-grafted-2-acrylamido-2-methyl-1-propane sulfonic acid (CP-g-AMPS) hydrogels for orally controlled drug delivery. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) were used to validate ellagic acid inclusion complexes and hydrogels. There was slightly higher swelling and drug release at pH 1.2 (42.20% and 92.13%) than at pH 7.4 (31.61% and 77.28%), respectively. Hydrogels had high porosity (88.90%) and biodegradation (9.2% per week in phosphate-buffered saline). Hydrogels were tested for their antioxidant properties in vitro against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). Additionally, the antibacterial activity of hydrogels was demonstrated against Gram-positive bacterial strains (Staphylococcus aureus and Escherichia coli) and Gram-negative bacterial strains (Pseudomonas aeruginosa).