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. 2023 May 16;14(5):278.
doi: 10.3390/jfb14050278.

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

Chengqun Yu  1 , Abid Naeem  1 , Yali Liu  2   3 , Yongmei Guan  1
Affiliations

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

Chengqun Yu et al. J Funct Biomater. .

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).

Keywords: anti-oxidants; bioavailability; hydrogels; inclusion complexation; phytoconstituents; polyphenol.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Proposed chemical structure of CP-g-AMPS hydrogels.
Figure 2
Figure 2
FTIR spectra of ellagic acid, EIC, HP-βCD, physical mixture (PM), CP, AMPS, EGDMA, unloaded, and EIC-loaded hydrogels.
Figure 3
Figure 3
TGA of ellagic acid, HP-βCD, EIC, CP, AMPS, unloaded, and loaded hydrogels.
Figure 4
Figure 4
DSC thermogram of EIC, ellagic acid, AMPS, HP-βCD, CP, unloaded, and drug-loaded hydrogels.
Figure 5
Figure 5
XRD of PM (physical mixture), EIC, CP, AMPS, HP-βCD, ellagic acid, EIC-loaded, and unloaded hydrogels.
Figure 6
Figure 6
SEM micrographs of synthesized hydrogel at (A) 2800× from one angle, (B) 2800× from another angle, (C) 6000× from one side, and (D) 6000× from another side.
Figure 7
Figure 7
Influence of different concentrations of (A) CP, (B) AMPS, and (C) EGDMA on the sol–gel and porosity properties of CP-g-AMPS hydrogels.
Figure 8
Figure 8
Influence of varying amounts of (A) CP (KAE-7,8,9), (B) AMPS (KAE-4,5,6), and (C) EGDMA (KAE-1,2,3) on the biodegradation of CP-g-AMPS hydrogels.
Figure 9
Figure 9
Effect of varying concentrations of components on hydrogels when swollen at pH 1.2 (A); CP, (B); AMPS, (C); EGDMA, (D); physical appearance and when hydrogels are swollen at pH 7.4 (E); CP, (F); AMPS, (G); EGDMA, and (H); physical appearance.
Figure 10
Figure 10
The drug release curve of CP-g-AMPS hydrogels and effect of components ((A); CP, (B); AMPS, and (C); EGDMA on release at pH 1.2 and at ((D); CP, (E); AMPS, and (F); EGDMA at pH 7.4.
Figure 11
Figure 11
A comparison of the antioxidant properties of CP-g-AMPS hydrogels by using (A) DPPH and (B) ABTS (* p < 0.05, ** p < 0.01, *** p < 0.001).
Figure 12
Figure 12
The zones of inhibition of samples against different bacterial strains.
See this image and copyright information in PMC

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