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. 2023 Mar 20;9(3):246.
doi: 10.3390/gels9030246.

Study of Hydroxypropyl β-Cyclodextrin and Puerarin Inclusion Complexes Encapsulated in Sodium Alginate-Grafted 2-Acrylamido-2-Methyl-1-Propane Sulfonic Acid Hydrogels for Oral Controlled Drug Delivery

Abid Naeem  1 , Chengqun Yu  1 , Weifeng Zhu  1 , Zhenzhong Zang  1 , Yongmei Guan  1
Affiliations

Study of Hydroxypropyl β-Cyclodextrin and Puerarin Inclusion Complexes Encapsulated in Sodium Alginate-Grafted 2-Acrylamido-2-Methyl-1-Propane Sulfonic Acid Hydrogels for Oral Controlled Drug Delivery

Abid Naeem et al. Gels. .

Abstract

Puerarin has been reported to have anti-inflammatory, antioxidant, immunity enhancement, neuroprotective, cardioprotective, antitumor, and antimicrobial effects. However, due to its poor pharmacokinetic profile (low oral bioavailability, rapid systemic clearance, and short half-life) and physicochemical properties (e.g., low aqueous solubility and poor stability) its therapeutic efficacy is limited. The hydrophobic nature of puerarin makes it difficult to load into hydrogels. Hence, hydroxypropyl-β-cyclodextrin (HP-βCD)-puerarin inclusion complexes (PIC) were first prepared to enhance solubility and stability; then, they were incorporated into sodium alginate-grafted 2-acrylamido-2-methyl-1-propane sulfonic acid (SA-g-AMPS) hydrogels for controlled drug release in order to increase bioavailability. The puerarin inclusion complexes and hydrogels were evaluated via FTIR, TGA, SEM, XRD, and DSC. Swelling ratio and drug release were both highest at pH 1.2 (36.38% swelling ratio and 86.17% drug release) versus pH 7.4 (27.50% swelling ratio and 73.25% drug release) after 48 h. The hydrogels exhibited high porosity (85%) and biodegradability (10% in 1 week in phosphate buffer saline). In addition, the in vitro antioxidative activity (DPPH (71%), ABTS (75%), and antibacterial activity (Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa) indicated the puerarin inclusion complex-loaded hydrogels had antioxidative and antibacterial capabilities. This study provides a basis for the successful encapsulation of hydrophobic drugs inside hydrogels for controlled drug release and other purposes.

Keywords: antioxidant; flavonoids; hydrogel; inclusion complexes; oral formulation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 8
Figure 8
The appearance of synthesized hydrogels at pH 1.2 (A) and pH 7.4 (B). Hydrogel swelling curves over time at pH 1.2 (C) and 7.4 (D).
Figure 9
Figure 9
In vitro drug release of SA-g-AMPS hydrogels at pH 1.2 (A) and 7.4 (B).
Figure 1
Figure 1
1H NMR spectra of puerarin and HP-βCD inclusion complexes (A), and FTIR spectra of pure components and hydrogels (B).
Figure 2
Figure 2
TGA of HP-βCD, puerarin, sodium alginate, AMPS, PIC, unloaded and PIC-loaded hydrogels.
Figure 3
Figure 3
The DSC of puerarin, HP-βCD, SA, PIC, AMPS, unloaded, and PIC-loaded hydrogels.
Figure 4
Figure 4
The XRD pattern of the formulation ingredients, inclusion complexes, and hydrogels synthesized.
Figure 5
Figure 5
SEM images of HP-βCD (A), puerarin (B), PIC (C), unloaded hydrogels at 400× (D), and PIC-loaded hydrogels at 400× (E).
Figure 6
Figure 6
Effect of sodium alginate (A), AMPS (B), and EGDMA (C) on sol–gel fraction and porosity of fabricated hydrogels.
Figure 7
Figure 7
Effect of ingredients on the biodegradation of hydrogels: sodium alginate (SAE-7,1,9) (A), AMPS (SAE-4,1,6) (B), and EGDMA (SAE-1,2,3) (C) on the in vitro biodegradation of the developed hydrogels.
Figure 10
Figure 10
Antioxidation effect of SA-g-AMPS hydrogels against DPPH (A) and ABTS (B). Here, * shows the p value < 0.05, ** p < 0.01, and *** p < 0.001.
Figure 11
Figure 11
Antibacterial effects (zone of inhibition) of SA-g-AMPS hydrogels.
Figure 12
Figure 12
The proposed chemical structure of the synthesized SA-g-AMPS hydrogels.
See this image and copyright information in PMC

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